Curcumin blocks fibrosis in anti-Thy 1 glomerulonephritis through up-regulation of heme oxygenase 1

BACKGROUND: Induction of heme oxygenase 1 (HO-1) has been shown to be beneficial in a variety of pathologic settings. Curcumin, a polyphenolic compound, has antifibrotic effects in lung models of fibrosis, and is known to induce HO-1 in renal tubular cells. In this study, we determined whether curcumin has antifibrotic properties in glomerular fibrosis and if these effects are mediated by induction of HO-1. METHODS: Curcumin effects on HO-1 expression in cultured mesangial cells and in glomeruli in vivo were analyzed by Northern and Western blotting. The dose-dependent effect of curcumin on glomerular fibrosis was tested in the anti-Thy 1 glomerulonephritis model. Curcumin was applied at doses of 10 to 200 mg/kg body weight by intraperitoneal injection from days 3 to 5 after induction of disease. On day 6, glomeruli were harvested and markers of fibrosis [plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta (TGF-beta), fibronectin, periodic acid-Schiff (PAS) staining] were analyzed. The effect of HO-1 inhibition was tested in a second experiment were nephritic rats were treated with curcumin (100 mg/kg body weight) or the combination of curcumin and the HO-1 inhibitor zinc protoporphyrin (100 microg/kg). RESULTS: Curcumin potently induced mesangial cell HO-1 expression in vitro and up-regulated glomerular HO-1 expression in nephritic animals in vivo. Curcumin treatment led to a significant, dose-dependent reduction of markers of fibrosis and proteinuria, with maximal inhibition at doses of 50 to 100 mg/kg. Beneficial effects of curcumin on markers of fibrosis and proteinuria were lost after HO-1 inhibition. CONCLUSION: Curcumin has antifibrotic effects in glomerular disease, which are mediated through an induction of HO-1.     

In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung

BACKGROUND: Idiopathic pulmonary fibrosis is a devastating disorder for which there is no effective treatment. Transforming growth factor (TGF)-beta plays a critical role in provoking fibrosis. Interleukin (IL)-10 is a potent immunosuppressive cytokine but its effect on the fibrosing process is unclear. A study was undertaken to examine whether IL-10 affects the production and activation of TGF-beta and thus can attenuate the fibrosis. METHODS: Mice were given an intratracheal injection of bleomycin. On day 1 or 14, IL-10 gene was delivered by rapid intravenous injection of Ringer's solution containing plasmid. Two weeks after the plasmid injection the mice were examined for fibrosis. The effect of IL-10 on TGF-beta production by alveolar macrophages was assessed. RESULTS: Even when delivered during the fibrosing phase, IL-10 gene significantly suppressed the pathological findings, hydroxyproline content, and production of both active and total forms of TGF-beta1 in the lung. Immunohistochemical analyses showed that alveolar macrophages were one of the major sources of TGF-beta1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed the expression of alphaV beta6 integrin, a molecule that plays an important role in TGF-beta activation, on lung epithelial cells. Alveolar macrophages from bleomycin injected mice produced TGF-beta1 spontaneously ex vivo, which was significantly suppressed by treatment of the mice in vivo or by treatment of the explanted macrophages ex vivo with IL-10. CONCLUSION: IL-10 suppresses the production and activation of TGF-beta in the lung and thus attenuates pulmonary fibrosis, even when delivered in the chronic phase.     

Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats

BACKGROUND: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis. METHODS: Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue. RESULTS: Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin. CONCLUSIONS: A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.     

Paraquat induced pulmonary fibrosis in three survivors.

Pulmonary lesions following paraquat poisoning are believed to be almost invariably fatal. The three patients reports here survived despite persistent radiological change. One of the patients died after taking a larger dose of paraquat one year later, and at necropsy histological changes attributable to the two episodes of paraquat poisoning were apparent.     

无精子症和生精功能正常者睾丸组织中血红素加氧酶的表达与差异性研究

目的:对人类睾丸组织中表达血红素加氧酶(HO)的细胞进行定位;通过测定原发性无精子症及梗阻性无精子症患者睾丸组织中血红素加氧酶1(HO-1)的表达量与正常睾丸组织中HO-1表达量的差异性,来探讨其与无精子症发病的相关性。方法:应用免疫组化方法对人类睾丸组织中表达HO的细胞进行定位;采用逆转录-荧光定量PCR(FQ-PCR)方法定量检测无精子症患者与正常人睾丸组织HO-1及HO-2基因水平的表达量;应用W est-ern印迹检测各组之间HO蛋白水平表达量。结果:在正常睾丸组织,HO-1主要表达在支持细胞上;而HO-2在支持细胞和各级生精细胞中均有表达;FQ-PCR结果显示非梗阻性无精子症患者睾丸组织HO-1、HO-2的表达量均显著低于正常组及梗阻性无精子症组(P<0.05),差异具有统计学意义。而梗阻性无精子症患者睾丸组织表达HO-1、HO-2的量与正常组相比无显著性差异。W estern印迹结果显示HO-1蛋白水平的表达量差异与基因水平一致。而HO-2的蛋白水平在各组之间表达没有显著性差异。结论:非梗阻性无精子症患者睾丸组织中HO的表达量显著性降低,且HO-1无论是蛋白水平还是基因水平的差异一致。HO-1可以通过抗炎、抗氧化、抗凋亡的机制保护睾丸组织免受各种应激的损伤,从而维护正常的生精功能。可见,HO-1的减少可能与生精功能低下相关,这可能是非梗阻性无精子症的发病机制之一。     

血红素氧合酶在糖尿病大鼠阴茎海绵体的表达

目的 检测血红素氧合酶1和2( HO-1/HO-2)在糖尿病(DM)大鼠阴茎海绵体(CC)的表达变化,探讨其在糖尿病相关勃起功能中的作用.方法 SD雄性大鼠50只,随机取30只制作糖尿病模型,余20只为正常对照.4周和8周后用阿扑吗啡试验评价大鼠勃起功能;免疫组织化学法及Western blot法检测HO-1、HO-2在大鼠CC内的表达部位及水平.结果 DM大鼠勃起次数在4周(2.17±0.94)和8周(0.85±1.07)时与对照组[4.0±1.15(4周);4.2±1.32(8周)]比均下降(P＜0.01),HO-1在4周(32.87±3.22)和8周(20.65±2.34)时的表达高于相应对照组[13.52±3.25(4周);12.35±2.29(8周)],P＜0.01,但8周较4周表达降低(P＜0.01),HO-2在4周(14.32±1.21)和8周(8.82±2.35)时的表达均低于相应对照组[20.91±2.07(4周);21.02±2.10(8周)],P＜0.01,且随时间逐渐加重(P＜0.01);对照组间差异无统计学意义(P＞0.05).结论 糖尿病造成大鼠勃起功能下降,可能与HO在DM大鼠CC内的表达降低密切相关.     

Attenuation of oxidative injury after induction of experimental intracerebral hemorrhage in heme oxygenase-2 knockout mice

OBJECT: Experimental evidence suggests that hemoglobin degradation products contribute to cellular injury after intracerebal hemorrhage (ICH). Hemoglobin breakdown is catalyzed in part by the heme oxygenase (HO) enzymes. In the present study, the authors tested the hypothesis that HO-2 gene deletion is cytoprotective in an experimental ICH model. METHODS: After anesthesia was induced with isoflurane, 3- to 6-month-old HO-2 knockout and wild-type mice were stereotactically injected with 15 microl autologous blood and a group of control mice were injected with an equal volume of sterile saline. Striatal protein and lipid oxidation were quantified 72 hours later using carbonyl and malondialdehyde assays. Cell viability was determined by performing a 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. Following blood injection, the investigators found a 3.4-fold increase in protein carbonylation compared with that in the contralateral striatum in wild-type mice; in knockout mice, the investigators found a twofold increase. The mean malondialdehyde concentration in injected striata was increased twofold in wild-type mice at this time, compared with 1.5-fold in knockout mice. Cell viability, as determined by MTT reduction, was reduced in injected striata to 38 +/- 4% of that in the contralateral striata in wild-type mice, compared with 66 +/- 5% in HO-2 knockout mice. Baseline striatal HO-1 protein expression was similar in wild-type and HO-2 knockout mice, but was induced more rapidly in the former after blood injection. CONCLUSIONS: Deletion of HO-2 attenuates oxidative cell injury after whole-blood injection into the mouse striatum. Therapies that specifically target HO-2 may improve outcome after ICH.     

The role of heme oxygenase in neuropathic and incisional pain

Heme oxygenase (HO) catalyzes the formation of free iron, biliverdin, and the second messenger molecule carbon monoxide from heme. We document a role for HO in both neuropathic and incisional pain models. For our neuropathic model, the L5 and L6 nerve roots of rats were ligated unilaterally resulting in mechanical allodynia and thermal hyperalgesia in the ipsilateral hind paws. Both changes were dose-dependently reversed by systemic administration of the HO inhibitor tin protoporphyrin (Sn-P). Likewise, a 1-cm incision made in one hind paw resulted in mechanical allodynia and thermal hyperalgesia, again reversible by using Sn-P. The 50% effective doses for Sn-P ranged from 4.0 to 6.8 micromol/kg depending on the model and nociceptive stimulus. We also observed that the blood-brain barrier impermeable HO inhibitor zinc protoporphyrin had little analgesic activity in these models when injected systemically. Using an enzymatic assay, we observed increased HO activity in lumbar spinal cord tissue from either nerve root ligated or incised animals as compared with tissue from sham-operated animals. Taken together, we interpret our results to indicate that an increase in spinal cord HO activity at least partially underlies the allodynia and hyperalgesia seen in rat models of neuropathic and incisional pain. IMPLICATIONS: Central nervous system heme oxygenase likely plays a role in nociceptive signaling in both neuropathic and incisional models of pain. Therefore, inhibitors of heme oxygenase activity may be viable analgesics in these settings.     

血红素加氧酶-1对器官移植保护作用的研究进展

血红素加氧酶-1(heme oxygenase,HO-1)是机体血红素降解过程的限速酶,它可将血红素分解为一氧化碳(CO)、游离铁和胆绿素.目前HO-1及其降解血红素的代谢产物体系在抗氧化、抗凋亡、抗炎症、舒张血管及细胞保护等方面的作用受到了普遍关注.HO-1在器官移植中的作用已成为研究热点,现就HO-1在器官移植中细胞保护作用的研究进展作如下综述.     

Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599

Summary Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1–3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU 51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p<0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p<0.01). Naloxone antagonized the anti-oedema effects and antinociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 posssibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.     

大鼠脊髓中血红素氧合酶基因的表达及其意义

目的观察正常大鼠脊髓中血红素氧和酶(H0)的表达和分布。方法雌性SD大鼠10只，按体重配成5对。每对随机分为正常组和诱导组，后者予以42℃热水浸泡躯体20min。取其中3对大鼠胸腰段脊髓，提取RNA后进行北方印迹分析；2对做免疫组织化学检测。结果HO-1探针检测到1．8kb mRNA，诱导组的丰度数倍于正常组。HO-2探针检测到两组标本都表达两种同源mRNA(1．3kb和1．9kb)，表达量相仿。免疫组织化学显示HO-1阳性细胞主要分布于前角神经元，诱导鼠中间带也可出现；HO-2阳性细胞散布于整个灰质中。结论HO参与脊髓信号传导和应激反应。     

小鼠肺纤维化CT影像自动分析方法

目的 基于CTAN软件建立小鼠肺纤维化(PF)CT影像自动分析方法并观察其自动分析效果。方法 将15只雄性c57小鼠随机分为博莱霉素组(A组)、博莱霉素+尼达尼布组(B组)及对照组(C组),每组5只。于建模第1、5、8、11及15天对A、B组采用腹腔注射博莱霉素构建PF模型,对C组以相同方法注射等量生理盐水;于第25、28、31及34天对B组腹腔注射尼达尼布以抑制PF。于第41天对所有小鼠行胸部CT扫描,并将图像导入CTAN软件,通过编辑和优化程序建立自动分析方法,提取肺CT影像区域,构建3D模型并进行数据分析;之后处死小鼠,取肺组织行Masson染色,观察肺部胶原沉积,评价PF Ashcroft评分,并检测肺羟脯氨酸含量,分析PF CT影像自动分析结果与Ashcroft评分及肺羟脯氨酸含量的一致性。结果 A组肺组织区域体积与肺区域体积比及肺区域CT值均高于C组(t=14.06、10.32,P均<0.01)和B组(t=11.22、8.29,P均<0.01);其肺羟脯氨酸含量和Ashcroft评分亦均高于C组(t=11.92、23.39,P均<0.01)和B组(t=7....     

Effect and mechanism of soluble epoxide hydrolase inhibitor in renal fibrosis mice model

Objective To investigate the effect and mechanism of soluble epoxide hydrolase inhibitor (sEHI) for NF-κB pathway and cell circle arrest of tubular epithelial cell in unilateral ureteral obstruction (UUO) mice model. Methods Thirty-two healthy C57BL/6 male mice performed UUO surgery to induce renal interstitial fibrosis. Animals were randomly divided into 4 groups: sham group (n=8), sEHI (1 mg?kg-1?d-1) group (n=8), UUO group (n=8) and UUO+sEHI (1 mg?kg-1?d-1) group (n=8). Daily sEHI [1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea, TUPS] or 2% DMSO was applied to mice by oral gavage from day 1 to day 14 after surgery. All mice were sacrificed at day 14 and kidneys were harvested for further analysis. The changes of renal tissue morphology and pathology were observed by Hematoxylin and eosin (HE) and sirius red staining. The expressions of sEH, nuclear factor κB p65 (NF-κB p65) and IκB were measured by Western blotting. The expressions of TNF-α, IL-1β, MCP-1, IL-6, TGF-β, CTGF, collagen-IV and α-SMA were analyzed by real-time PCR. Immunofluorescence staining of phospho-histone H3 (p-HH3) and Ki67 was performed to determine the stage of cell cycle G2/M arrest. Results The expression and activity of sEH increased in UUO group (P﹤0.05). Administration of sEHI inhibited activity of sEH and infiltration of inflammatory cell in tubular interstitial, as well as attenuated tubular damage and tubular interstitial fibrosis. Western blotting analysis revealed administration of sEHI inhibited up-regulated NF-κB p65 and down-regulated IκB in UUO group (P﹤0.05). Real-time PCR demonstrated that administration of sEHI obviously decreased the mRNA expression of cytokines and fibrosis markers, including of TNF-α, IL-1β, MCP-1, IL-6, TGF-β, CTGF, Collagen-IV, α-SMA (P﹤0.05). Immunofluorescence staining showed that there were much more p-HH3 and Ki67 double positive nuclear tubular epithelial cells and interstitial cells in UUO group, compared with Sham group (P﹤0.05). Administration of sEHI reduced the number of double positive nuclear cell only in tubular epithelial cells (P﹤0.05), but not in interstitial cells. Conclusions In UUO tubular interstitial fibrosis model, sEHI inhibits the activation of NF-κB pathway by down-regulating p65 and up-regulating IκB and ameliorates the infiltration of inflammatory cells. In addition, sEHI plays anti-fibrosis effect by moderating cell cycle G2/M arrest and reducing the excrete of pro-fibrosis factors of tubular epithelial cells.     

Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis

BACKGROUND: Heme oxygenase (HO)-1, long believed to be a cytoprotective protein, has recently been identified as a graft survival gene. This study evaluates the role of HO-1 in a murine heterotopic tracheal allograft model for obliterative bronchiolitis. METHODS: Mice with deficient or experimentally enhanced HO-1 expression underwent subcutaneous implantation of murine tracheal isografts and allografts. Grafts were excised after 9, 16, or 21 days and evaluated by histologic examination, immunohistochemistry for HO-1 and interleukin (IL)-10 proteins, and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. To evaluate the relationships between IL-10 and HO-1, the effects of modulation of HO-1 expression on IL-10 expression were evaluated and HO-1 expression was examined in tracheal transplants from IL-10 null mice. RESULTS: Isografts demonstrated normal histology with minimal HO-1 staining, whereas allografts showed features of human airway rejection (loss of respiratory epithelium, luminal granulation tissue, lymphocytic tracheitis) with increased HO-1 staining in macrophages and mesenchymal cells. HO-1-deficient mice demonstrated a more rapid progression of the tracheal allograft injury as compared with control allografts, and this was associated with a decrease in the anti-inflammatory cytokine, IL-10. Tracheal transplants using IL-10-deficient mice also resulted in a more severe injury, and this was accompanied by a decrease in HO-1 staining. CONCLUSIONS: HO-1 protein expression is increased in murine heterotopic airway rejection, and deficiency of HO-1 accelerates the development of the obliterative bronchiolitis-like lesion. IL-10 protein expression parallels expression of HO-1, suggesting that IL-10 may participate in the genesis of HO-1's effects on the inflammatory processes triggered by allotransplantation.     

Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist

BACKGROUND: Signalling of angiotensin II via angiotensin II type 1 receptor (AT1) promotes cardiac and renal fibrosis, but its role in lung fibrosis is little understood. Using a rat bleomycin (BLM) induced model of pulmonary fibrosis, we examined the expression of AT1 in the lung and the effect of an AT1 antagonist on pulmonary fibrosis. METHODS: Adult male Sprague-Dawley rats were given 0.3 mg/kg BLM intratracheally. Two days earlier they had received 10 mg/kg/day of the AT1 antagonist candesartan cilexetil mixed in the drinking water. AT1 expression in the lungs was examined by immunohistochemistry and immunoblot methods. The effect of the AT1 antagonist on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and hydroxyproline assay. RESULTS: Immunohistochemical studies showed overexpression of AT1 in inflammatory immune cells, alveolar type II cells, and fibroblasts. A quantitative assay for AT1 showed that AT1 expression was significantly upregulated in cells from BAL fluid after day 3 and in the lung homogenates after day 21. Candesartan cilexetil significantly inhibited the increase in total protein and albumin, as well as the increase in total cells and neutrophils in BAL fluid. On day 21 candesartan cilexetil also ameliorated morphological changes and an increased amount of hydroxyproline in lung homogenates. In addition, BLM increased the expression of transforming growth factor (TGF)-beta1 in BAL fluid on day 7; this increase was significantly reduced by candesartan cilexetil. CONCLUSION: AT1 expression is upregulated in fibrotic lungs. Angiotensin II promotes lung fibrosis via AT1 and, presumably, in part via TGF-beta1.     

Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice

BackgroundWe tested the hypothesis that vardenafil, a common drug used for improving erectile dysfunction and able to partially normalize transepithelial chloride transport in cystic fibrosis (CF), modulates CF lung inflammation.MethodsInflammatory markers in lungs of F508del-CF and wild-type mice were monitored in response to lipopolysaccharide from Pseudomonas aeruginosa (LPS). The effect of pretreatment with vardenafil (0.14 mg/kg) was evaluated.ResultsA latent inflammatory status, characterized by neutrophil infiltrate, mouse macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-α, was found in baseline conditions in F508del-CF mice. Inflammatory markers were increased after LPS with higher responses in CF. Vardenafil globally attenuated inflammatory responses in both genotypes however reduction of macrophage infiltration, macrophage chemoattractant chemokine and interleukin-1β was observed in the CF group only.ConclusionVardenafil reduces lung inflammation with a more pronounced effect in F508del-CF mice, particularly on macrophage cell markers.     

Reduction of bleomycin induced lung fibrosis by transforming growth factor β soluble receptor in hamsters

BACKGROUND: Transforming growth factor beta (TGF-beta) is a key mediator of collagen synthesis in the development of lung fibrosis. It has previously been shown that the administration of TGF-beta antibody and TGF-beta binding proteoglycan, decorin, reduced bleomycin (BL) induced lung fibrosis in animals. The present study was carried out to investigate whether intratracheal instillation of TGF-beta soluble receptor (TR) would minimise the BL induced lung fibrosis in hamsters. METHODS: The effect of a recombinant TR (TGFbetaRII) on the lung collagen accumulation was evaluated in a BL hamster model of pulmonary fibrosis. Animals were divided into four groups and intratracheally injected with saline or BL at 6.5 U/4 ml/kg followed by intratracheal instillation of phosphate buffered saline (PBS) or 4 nmol TR in 0.3 ml twice a week. Twenty days after the first intratracheal instillation the hamsters were killed for bronchoalveolar lavage (BAL) fluid, biochemical, and histopathological analyses. RESULTS: Treatment of hamsters with TR after intratracheal instillation of BL significantly reduced BL induced lung fibrosis as shown by decreases in the lung hydroxyproline level and prolyl hydroxylase activity, although they were still significantly higher than those of the saline control. Histopathological examination showed a considerable decrease in BL induced fibrotic lesions by TR treatment. However, TR did not prevent the BL induced increases in total cells and protein in the BAL fluid. CONCLUSIONS: These results suggest that TR has antifibrotic potential in vivo and may be useful in the treatment of fibrotic diseases where increased TGF-beta is associated with excess collagen accumulation.     

血红素氧化酶-1功能和调节及其在脊髓损伤中作用的研究进展

脊髓损伤作为一种严重的中枢神经系统创伤性疾病,一直是医学界有待于攻克的难题。据统计全世界每年有新发生脊髓损伤患者约50万,而其中截瘫患者总数可达250万人。脊髓损伤的最终结局由原发性机械损伤以及受损后一系列生化因素引起的继发性损伤共同决定。原发性机械损伤是一个不可逆转的过程,而对继发性损伤的控制水平直接影响最终的损伤程度和临床预后。