Toll样受体4与肾脏疾病研究进展

Toll样受体4(Toll-like receptor 4,TLR4)是一种模式识别受体,是链接固有免疫和获得性免疫的桥梁,在免疫系统的调节中有重要作用,它可通过激活信号转导通路、促进炎症因子表达等诱发炎症反应.TLR4不仅表达于各种免疫细胞表面,还在肾小球系膜细胞、肾小管上皮细胞等都有广泛表达.近年来,TLR4在肾脏疾病中的作用受到越来越多的关注,本文就TLR4在肾缺血再灌注损伤、糖尿病肾病、急性肾损伤以及尿路感染等肾脏疾病中的作用作一综述.     

Toll样受体与脓毒症的研究进展

脓毒症系感染引起的全身性炎症反应 ,进一步可发展为脓毒性休克和多器官功能障碍综合征 ,是严重创、烧伤患者死亡的主要原因之一 ,但其确切的发病机制迄今尚未完全阐明。以往研究表明 ,多种病原微生物的细胞壁成分 [如革兰阴性菌的内毒素(ＬＰＳ)、革兰阳性菌的肽聚糖 (ＰＧＮ     

异丙酚对LPS诱导中性粒细胞Toll样受体2和Toll样受体4表达的影响

目的 探讨异丙酚对内毒素(LPS)诱导中性粒细胞Toll样受体2(TLR2)和TLR4表达的影响.方法 健康志愿者6名,年龄20～35岁,各采集外周静脉血样50 ml,加入20 U/ml肝素抗凝,分离提纯中性粒细胞,制备细胞悬液,然后随机分为6组,每组6皿:对照组(C组)不给予任何药物,置于37℃、5%CO_2培养箱中培养12 h;异丙酚脂质溶剂intralipid组(I组)、异丙酚组(P组)和LPS组(L组):分别加入intralipid(终浓度为5 μg/ml)、异丙酚(终浓度为5 μg/ml)或LPS(终浓度为1μg/ml),置于37℃、5%CO_2培养箱中孵育12 h;intralipid+LPS组(IL组)和异丙酚+LPS组(PL组)先分别加入intralipid(终浓度为5 μg/ml)或异丙酚(终浓度为5 μg/ml)后,置于37℃、5%CO_2培养箱中孵育20 min,然后加入LPS(终浓度为1μg/ml),置于37℃、5%CO_2培养箱孵育12 h.采用流式细胞仪测定中性粒细胞膜TLR2和TLR4的表达;采用荧光定量PGR检测中性粒细胞膜TLR2 mRNA和TLR4 mRNA的表达;采用ELISA法测定培养上清液TNF-α和IL-8的浓度.结果 与C组比较,I组和P组TLB2和TLR4的表达、1NF-α和IL-8L-8的浓度差异无统计学意义(P>0.05),L组和IL组TLR2和TLR4的表达上调,L组TNF-α和IL-8L-8的浓度升高,IL组IL-8浓度升高(P<0.05);与L组比较,IL组TLR2和TLR4的表达、TNF-α和IL-8L-8的浓度差异无统计学意义(P>0.05),PL组TLR2和TLR4的表达下调,TNF-α和IL-8L-8的浓度降低(P<0.05).各组TLR2 mRNA和TLR4 mRNA的表达差异无统计学意义(P>0.05).结论 异丙酚可下调LPS诱导的中性粒细胞TLR2和TLR4的表达,从而抑制炎性反应.     

Toll样受体4研究进展

Toll样受体（Toll like receptor,TLR）是近几年发现的一类天然免疫受体,其分布十分广泛,主要表达于单核细胞、巨噬细胞、树突状细胞、多形核细胞、T淋巴细胞、B淋巴细胞及自然杀伤细胞等表面,属于模式识别受体（pattern recognition receptor,PRR）,可对病原体相关分子模式（pathogen associated moleeular patterns,PAMP）进行识别、结合,并引发一系列信号转导,进而导致炎性介质的释放,在天然免疫防御中起着重要作用,并最终激活获得性免疫系统。     

Toll样受体4的基因多态性与脓毒症

脓毒症是指机体感染微生物后发生的全身炎性反应综合征.在该疾病发生发展中是基因多态性影响着机体对该综合征的遗传易感性.其中Toll样受体4(toll-like receptor4,TLR4)作为识别病原微生物的主要受体之一,在自身免疫中起着重要的作用.已有研究表明TLR4的基因多态性与脓毒症的遗传易感性密切相关,其中TLR4基因的Asp299Gly和Thr399Ile位点的突变与脓毒症的发生发展及预后有关.现就TLR4的功能、信号转导通路及其基因多态性与脓毒症易感性的相关关系作一综述.     

脓毒症大鼠心肌Toll样受体4和髓样分化蛋白-2基因表达的变化和意义

目的探讨脓毒症大鼠心肌组织内毒素信号转导复合受体．Toll样受体4（TLR4）／髓样分化蛋白．2（MD2）基因表达的变化情况。研究其与心肌组织肿瘤坏死因子-α（TNF-α）基因表达的关系。方法采用腹腔注射5mg／kg体重内毒素（LPS）制作大鼠脓毒症模型。动物分为正常对照组（10只），内毒素注射后1、2、6h组（各10只），利用逆转录-聚合酶链反应（RT-PCR）方法检测心肌组织TLR4／MD2以及TNF-α的基因表达。结果LPS注射后1h，TLR4／MD-2及TNF-α基因表达开始升高，2h达高峰，6h逐渐下降，各时间点的表达均显著高于对照组（P〈0．01）。相关分析表明，心肌TUM／MD2基因表达分别与TNF-α基因表达呈显著正相关（P〈0．05）。结论LPS可上调心肌组织TLR4／MD-2基因表达并诱导早期炎症细胞因子TNF-α基因表达。TLR4识别LPS信号是以TLR4／MD-2复合受体的形式完成的。而且在识别过程中，MD-2是TLR4必需的作用分子。     

盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

目的 探讨盐酸戊乙奎醚对内毒索性急性肺损伤大鼠肺组织Toll样受体4(TLR4)mRNA和Toll样受体2(TLR2)mRNA表达的影响.方法 健康SD大鼠60只,雌雄不拘,体重200～220g,采用随机数字表法,将大鼠随机分为5组(n=12),对照组(C组)、LPS组和低、中、高剂量盐酸戊乙奎醚组(P1组～P3组).C组腹腔注射生理盐水2ml;LPS组腹腔注射LPS 8mg/kg;P1组～P3组分别腹腔注射LPS 8 mg/kg和盐酸戊乙奎醚0.3、1.0和3.0 mg/kg.给药结束后6 h时开胸,心室取血,并取肺组织,采用ELISA法测定血清TNF-α和Ib-6的浓度,RT-PCR法测定肺组织TLR4 mRNA和TLR2 mRNA 的表达水平,并观察肺组织病理学结果.结果 与C组比较,LPS组、P1组～P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均升高(P<0.05);与LPS组比较,P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05),P1组上述指标差异无统计学意义(P>0.05);与P1组比较,P2组和P1组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05);P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达比较差异无统计学意义(P>0.05).P2组和P3组肺组织病理学损伤程度明显轻于LPS组.结论 盐酸戊乙奎醚可通过下调肺组织TLR4 mRNA和耵JR2 mRNA的表达,降低炎性反应,从而减轻大鼠内毒素性急性肺损伤.

Abstract：

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.     

右美托咪啶对老年患者术后认知功能和围术期单核细胞Toll样受体2和Toll样受体4表达的影响

目的 探讨右美托咪啶对老年患者术后认知功能和围术期单核细胞Toll样受体2(TLR2)和TLR4表达的影响.方法 择期手术治疗的腰椎间盘突出症和腰椎骨折患者45例,年龄≥65岁,体重53～72 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将其随机分为3组(n=15):对照组(Ⅰ组)和不同剂量右美托咪啶组(Ⅱ组和Ⅲ组).麻醉诱导结束后静脉输注右美托咪啶负荷剂量1.0μg/kg,输注时间15 min,然后以0.5μg/·kg-1·h-1(Ⅱ组)或1.0 μg·Jg-1·h-1(Ⅲ组)的速率静脉输注至术毕,Ⅰ组给予等容量生理盐水.于麻醉诱导前(T1)、手术开始1.5 h(T2)、术毕(T3)和术后24 h(T4)时取静脉血样,检测外周血单核细胞TLR2及TLR4的表达.分别于术前1d和术后7d时采用简易精神状态量表评分和韦氏成人记忆量表及智力量表评价认知功能,记录术后认知功能障碍的发生情况.结果 与Ⅰ组比较,Ⅱ组和Ⅲ组术后认知功能障碍发生率降低,T2～T4时单核细胞TLR2和TLR4表达下调(P＜0.05);与Ⅱ组比较,Ⅲ组术后认知功能障碍发生率降低,T～T4时单核细胞TLR2和TLR4表达下调(P＜0.05).结论 右美托咪啶可预防老年患者POCD的发生,其机制与抑制单核细胞TLR2和TLR4的表达有关.     

盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.     

腹腔感染所致多器官损害与Toll样受体2基因表达的关系

目的　探讨Toll样受体 2 (TLR2 )基因表达与严重腹腔感染所致多器官损害的关系。方法　采用大鼠盲肠结扎穿孔 (CLP)模型造成脓毒症。将 80只大鼠随机分为正常对照组 (n =10 )、假手术组 (n =10 )和脓毒症组 (n =6 0 ) ,留取肝、肺、肾及小肠组织检测TLR2和肿瘤坏死因子 α(TNF α)mRNA表达 ,同时测定血浆中丙氨酸转氨酶 (ALT)、肌酐 (Cr)及肺组织髓过氧化物酶(MPO)、小肠组织二胺氧化酶 (DAO)活性。结果　CLP后 2～ 6h肝、肺、肾及小肠组织TLR2mR NA表达迅速增多 (P <0 .0 1) ,12h达高峰 (P <0 .0 1) ,分别为 0 .818± 0 .0 14 ,0 .95 5± 0 .0 31,0 .82 0± 0 .0 45 ,0 .885± 0 .0 18,并持续至伤后 72h。相关分析结果显示 ,肝、肺、小肠中TLR2与TNF α基因表达呈显著正相关 (P <0 .0 5 0 .0 1) ,肾组织内TLR2与TNF α基因表达无明显相关(P >0 .0 5 ) ;肝、肺、肾、小肠组织中TLR2基因表达分别与ALT、MPO、Cr、DAO水平显著相关。结论　严重腹腔感染可导致多种组织TLR2mRNA持续表达 ,其改变与多器官损害密切相关。     

Evaluation of the Effects of Laparotomy and Laparoscopy on the Immune System in Intra-Abdominal Sepsis—A Review

This review portrays the most common experimental models of intra-abdominal sepsis. Additionally, it outlines the facts that distinguish laparotomy from laparoscopy, in respect to the immune response, when comparing these two techniques in experimental models of intra-abdominal sepsis. It describes the consequences of pneumoperitoneum and trauma produced by laparoscopy or laparotomy, respectively, on bacterial translocation and immunity. Furthermore, we report the few efforts that have been made in clinical settings, where surgeons have attempted to utilize laparoscopy as a therapeutic module when treating peritonitis or sepsis of abdominal origin. Certainly there is a need for more research in order to fortify the role of pneumoperitoneum in sepsis of abdominal origin. It seems that minimally invasive surgery will inevitably gain acceptance by surgeons, as evidence points that by inflicting less trauma the healing response is expected to be more efficient, especially in septic patients.     

The effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats

GTP-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo biosynthesis of biopterin. The present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP),an inhibtor of GTP-CHI, on the development of postburn Staphylococcus aureus sepsis. Methods: 56 male Wistar rats were randomly divided into four groups as follows: normal control group (n= 10), scald control group(n= 10),pos tburn sepsis group (n= 20) and DA HP treatment group (n= 16). In the scald control group, rats were subjected to a 20% total body surface area (TBSA) Ⅲ° scald injury, then sacrificed at 24 hrs. In the postburn sepsis group (n=20), rats were inflicted with 20% TBSA Ⅲ° scald followed by Staphylococcus aureus challenge, and they were further divided into 2 and 6 hrs groups. In the DAHP treatment group (n= 16), animals were intraperitoneally injected with a dose of 1g/kg DAHP prior to Staphylococcus aureus challenge, and then further divided into 2, 6 hrs groups. Tissue samples from liver, kidneys, lungs and heart were collected to determine GTP-CHI, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression. Meanwhile, biopterin and nitric oxide (NO) levels in these tissues were also measured. Results: After the scald injury followed by Staphylococcus aureus challenge, GTP-CHI mRNA expression and biopterin levels significantly elevated in various tissues such as liver, heart, kidneys and lungs, so did the values of iNOS mRNA expression and NO formation (P＜0.01). Pretreatment with DAHP could significantly reduce GTP-CHI/biopterin induction (P＜0. 05～0. 01), and the up-regulation of iNOS/NO was also suppressed. Furthermore, DAHP administration could also inhibit the gene expression of TNF-α. 2 hrs after septic challenge, TNF-α mRNA expression in liver, kidneys and lungs in DAHP-treated group were 35.7%, 37.3% and 33.0% of those in postburn septic group, respectively. Additionally, in animals without DAHP treatment, the 6-hour mortality was 55.6% (20/36), while it was only 25.0% in DAHP-treated animals (4/16, P=0. 08). Conclusions: Early treatment with DAHP might be a potential strategy to prevent the development of postburn Staphylococcal sepsis, which appears to be associated with down-regulation of biopterin and NO formation by DAHP.     

新型光催化反应器降解典型有机污染物2,4-二硝基苯酚

利用ＴｉＯ２在Ｈ２Ｏ２中的溶解性，在玻璃表面形成ＴｉＯ２薄膜，制作了新型环状光催化型反应器。以２，４－二硝基苯酚为典型有机化合物，进行了降解的条件研究，并测试了反应器性能。分别考察了催化剂涂层载体、光源、搅拌以及流速对２，４－二硝基苯酚光降解的效率。结果表明：石英玻璃为最理想的光催化剂载体；水银灯对２，４－二硝基苯酚的降解速度最快，是理想的光源；搅拌能够提高反应器效率；采用适宜的流速（４５ｍｌ／ｍｉｎ）可使反应器效率达到理想值。在反应动力学研究中，２，４－二硝基苯酚的最大降解速率为Ｋｄｍａｘ＝０．３６ｍｇ／（Ｌｍｉｎ），最终的降解率达到９９．５％．     

The Effect of Platelet-Rich-Plasma on the Healing of Left Colonic Anastomosis in a Rat Model of Intra-Abdominal Sepsis

Objective: The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on the healing of colonic anastomosis in the presence of sepsis. Materials and Method: Fifty Wistar-albino male rats were used. Ten healthy rats were euthanized to prepare PRP, the rest were subjected to colonic anastomosis and randomly allocated into four groups of 10 rats each as anastomosis without PRP (C), without PRP in sepsis (SC), anastomosis with PRP (C-PRP), and with PRP in sepsis (S-PRP). Sepsis was induced by cecal ligation and puncture procedure. All animals were euthanized on postoperative day 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxyproline (TH) and histopathological examination of each group were analyzed by using one-way analysis of variance (ANOWA) and Tukey's HSD post-hoc test to assess the differences between the groups. Results: There was no statistical difference among the groups in terms of body weight changes. The ABP was measured at a mean value of 179.5 ± 10.3, 129.3 ± 14.2, 209 ± 14.4, and 167.5 ± 7.5 mm-Hg, in group C, SC, C-PRP, and S-PRP, respectively. The ABP and TH of C-PRP group was significantly higher than three groups (p < .05, for each comparison). In sepsis, PRP significantly raised the mean ABP and TH levels up to the levels of C group. Tissue regeneration was significant with increased collagen formation in C-PRP group than the other groups (p < .05). The healing effect of PRP in the presence of sepsis was significant than S-group (p < .05), while similar to C group (p = .181). Conclusion: PRP application to colonic anastomosis promotes the healing process in rats with intra-abdominal sepsis.     

血必净联合连续肾脏替代治疗对外科术后脓毒症患者炎性因子及凝血功能的影响

目的:探讨血必净联合连续肾脏替代治疗(CRRT)对外科术后脓毒症患者炎性因子与凝血功能的影响。方法:将2016年3月1日2018年12月1日本院ICU科所收治的术后脓毒症患者158例纳入此次研究,依据治疗方案的不同,分成对照组52例、血必净组53例与联合组(血必净+血液净化)53例,比较治疗前与治疗后48 h三组的血清炎性因子(CRP、LPS、PCT及IL-10、IL-6、IL-1b)、凝血功能(APTT、PT、FIB)、肾功能(血Scr与BUN)、氧合指数及APACHEⅡ评分。结果:治疗后,各组凝血功能相关指标、血清相关炎性因子、肾功能指标、氧合指数及APACHEⅡ评分与治疗前相比均有所改善(P<0.05),血必净组和联合组均比对照组改善明显,且联合组比血必净组更加显著(P<0.05)。结论:血必净与CRTT联合用于外科术后脓毒症的患者,能够有效降低患者机体发生的炎性反应,对患者的凝血功能与APACHEⅡ评分起到改善作用,有一定的临床推广价值。     

益肾胶囊对糖尿病肾病大鼠肾组织SOCS-3、TLR4、IL-6表达的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠模型肾组织中细胞因子信号抑制物3（SOCS-3）、Toll样受体4（TLR4）及白细胞介素-6（IL-6）表达的影响。方法：将40只Wistar系雄性大鼠随机分为4组,即：正常对照组（N组）、DN模型组（DN组）、DN模型＋益肾胶囊治疗组（DN＋Y组）及DN模型＋氯沙坦钾治疗组（DN＋L组）,利用单侧肾切除＋腹腔注射链脲佐菌素,建立DN大鼠模型。记录大鼠体重,检测血糖、24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）等指标;取肾组织行HE染色,进行病理组织学观察;用免疫组化方法检测肾组织中SOCS-3、TLR4及IL-6的表达。结果：12周末,DN组大鼠的24h尿蛋白定量、Scr、BUN均高于N组（P〈0.05）,肾组织中SOCS-3、TLR4及IL-6表达水平明显高于N组（P〈0.05）;DN＋Y组大鼠24h尿蛋白定量、Scr、BUN均低于DN组（P〈0.05）,肾组织SOCS-3表达水平明显高于DN组（P〈0.05）,而TLR4及IL-6表达水平明显低于DN组（P〈0.05）;DN＋L组与DN＋Y组24h尿蛋白定量、Scr、BUN、SOCS-3、TLR4及IL-6的差异无统计学意义（P〉0.05）。结论：益肾胶囊可能通过调节SOCS-3、TLR4及IL-6在肾组织中的表达,降低DN的炎症反应,从而延缓DN的进展。     

氯沙坦钾对大鼠腹膜透析模型腹膜纤维化组织中TLR4表达的影响

目的：探讨氯沙坦钾对大鼠腹膜透析模型腹膜纤维化组织中TLR4、IL-6、IL-8表达的影响。方法：30只雄性SD大鼠随机分为正常对照组、腹膜纤维化模型组（模型组）、氯沙坦钾治疗组（治疗组）,每组各10只。正常对照组不予任何干预,模型组给予4.25%腹膜透析液腹腔注射（100ml·kg^-1·d^-1）,治疗组给予4.25%腹膜透析液腹腔注射（100ml.kg-1.d-1）,同时给予氯沙坦钾片灌胃（30mg·kg^-1·d^-1）,于4周末杀检大鼠,做腹膜平衡试验,准确量取超滤量,留取0和4h血清与腹腔流出液标本,计算葡萄糖转运量,4h后,取壁层腹膜组织作形态学观察,用免疫荧光的方法检测TLR4、IL-6、IL-8在脏层腹膜组织中的表达。结果：与正常对照组比较,模型组大鼠壁层腹膜厚度明显增厚（P〈0.01）,超滤量下降（P〈0.01）,葡萄糖转运量升高（P〈0.01）。与模型组相比较,氯沙坦钾治疗后大鼠壁层腹膜变薄（P〈0.01）,超滤量增加（P〈0.01）,葡萄糖转运率量下降（P〈0.01）;正常腹膜组织中TLR4、IL-6、IL-8在间皮细胞中呈弱表达,模型组与正常组相比,TLR4、IL-6、IL-8表达明显增多;治疗组与模型组相比,TLR4、IL-6、IL-8蛋白表达明显下调。结论：氯沙坦钾能够下调腹膜纤维化大鼠腹膜组织TLR4、IL-6、IL-8表达水平,改善腹膜的超滤和转运功能。     

益肾胶囊对糖尿病肾病大鼠模型肾组织TLR4表达的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠模型肾组织Toll样受体4（toll-like receptor4,TLR4）、白细胞介素-6（IL-6）及白细胞介素-8（IL-8）表达水平的影响。方法：36只Wistar雄性大鼠随机分成正常对照组、DN模型组、益肾胶囊治疗组,每组12只,利用单侧肾切除加腹腔注射链脲佐菌素建立DN大鼠模型,连续给药12周。记录大鼠体重、观察24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）变化;取肾组织行病理组织学观察;用免疫荧光方法检测肾组织中TLR4、IL-6及IL-8的表达水平的变化。结果：12周末,DN模型组大鼠的24h尿蛋白定量、Scr、BUN均高于正常对照组（P〈0.05）,肾组织中TLR4、IL-6及IL-8表达水平明显高于正常对照组（P〈0.05）;益肾胶囊治疗组大鼠24h尿蛋白定量、Scr、BUN均低于模型组（P〈0.05）,肾组织TLR4、IL-6及IL-8表达水平明显低于DN模型组（P〈0.05）。结论：益肾胶囊可能通过调节肾组织TLR4、IL-6及IL-8的表达,减少DN的炎症反应,从而延缓了DN的进展。     

The Role of Complement,C5a and Its Receptors in Sepsis and Multiorgan Dysfunction Syndrome

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.     

加味大柴胡汤对阻塞性黄疸大鼠TLR4表达的影响

目的 探讨加味大柴胡汤在临床上辅助治疗阻塞性黄疸的理论机制.方法 制作阻塞性黄疸大鼠模型,分为7、14、21 d共3个时段,每个时段分3组,即:(1)假手术+生理盐水组(SO+NS组);(2)胆总管结扎+生理盐水组(BDL+NS组);(3)胆总管结扎+加味大柴胡汤组(BDL+MMDB组).每组6只SPF级SD大鼠,在各时段取大鼠肝组织及下腔静脉血,检测AST、ALB及TB;用RT-PCR检测,TLR4 mRNA的表达.结果 胆总管结扎7 d时,BDL+MMDB组与BDL+Ns组外周血TB、AST比SO组均上升,且后者明显.BDL+MMDB组与SO组及BDL+NS组相比,差异均有统计学意义(P<0.01).胆总管结扎14、21 d时,BDL+MMDB组与BDL+Ns组外周血TB、AST持续升高,且后者增高更明显.BDL+MMDB组与SO组及BDL+Ns组相比,差异均有统计学意义(P<0.01).正常肝组织中TLR4mRNA的表达不明显.胆总管结扎7、14、21 d时,BDL+MMDB组与BDL+Ns组TLR4 mRNA表达持续显著增加,且后者增加更明显.同时段中BDL+MMDB组与S0组相比、BDL+MMDB组与BDL+NS组相比,差异均有统计学意义(P<0.01).结论 加味大柴胡汤可以通过降低肝组织中TLR4,从而减轻内毒素所致肝脏的损伤.