虾青素对创伤性颅脑损伤保护作用的研究进展

创伤性颅脑损伤（TBI）致死、致残率高,严重危害人类健康,TBI后的继发级联损伤是导致患者预后不良的重要原因。有效地治疗继发性脑损伤是降低TBI致残率,改善患者预后,提高生活质量的重要环节。虾青素（ATX）是一种天然的类胡萝卜素,具有多种生物学活性。许多研究表明了ATX在对抗中枢神经系统急慢性损伤中产生的氧化应激、炎症反应以及改善颅脑灌注、保护神经等方面有良好作用。本文针对ATX对TBI的保护作用机制及研究进展综述如下。     

虾青素对高脂血症大鼠脂代谢的影响

目的研究虾青素对高脂饲料喂养下大鼠诱发高脂血症过程中血脂代谢的干预作用。方法将60只SD雄性大鼠,随机分为正常对照组、高血脂模型组、辛伐他汀阳性药组(200 mg/kg)、虾青素高、中、低剂量组(415、210、110 mg/kg),分别饲喂标准、高脂、高脂+辛伐他汀、高脂+虾青素,于实验开始前1 d和开始后第4、8、12周末取空腹血,检测血清甘油三酯(TG)、总胆固醇(TC)和高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)。结果与高血脂模型组比较,虾青素组的TC、TG、LDL-C在8、12 w时降低,差异显著(P<0.01),而HDL-C升高,差异显著(P<0.01)。结论虾青素可以对高脂饲料喂养大鼠诱发高脂血症过程中的血脂代谢产生影响,改善血脂变化。     

低频脉冲超声对骨关节炎中软骨细胞的影响

超声被广泛应用于临床的诊断和治疗,但是临床上低频脉冲超声(LIPU)的应用却非常有限。在实验中,LIPU的应用却是很广泛。在许多的动物实验中证实,LIPU对许多结缔组织疾病有一定疗效。骨关节炎(OA)是以关节软骨细胞、细胞外基质、软骨下骨等合成与分解代谢失衡,关节软骨损坏为特征的全关节疾病。     

虾青素防治冠心病作用机制的研究进展

心血管病死亡率占我国主要疾病死因首位,其中冠心病是临床最常见死亡原因之一。虾青素因其独特结构被认为是一种适合预防及治疗冠心病的药物。本文对近年来虾青素在防治冠心病方面的研究进展,包括抗氧化、抗炎、降压、改善糖代谢、调节脂代谢和心肌梗死后保护作用作一综述。     

骨关节炎关节软骨细胞基因表达谱的芯片研究

目的 利用基因芯片技术,研究骨关节炎关节软骨细胞基因表达谱差异性基因、差异性基因功能及通路,初步探讨骨关节炎预警基因.方法 入选行关节置换术的骨关节炎、类风湿关节炎(RA)和无关节炎的创伤患者各3例,分成骨关节炎组、RA组和创伤组.分别取关节软骨标本,体外培养关节软骨细胞.采用人类全基因组寡核苷酸微阵列芯片技术,通过微阵列差异性基因分析软件两因素不配对检验分析比较骨关节炎组分别与创伤组、RA组关节软骨细胞基因表达谱的差异在生物分子功能注释系统中分析差异性基因功能、通路.结果 骨关节炎组与创伤组比较差异基因为145个(其中70个上调,75个下调),骨关节炎组与RA组比较差异基因为281个(其中94个上调,187个下调);骨关节炎组分别与创伤组、RA组比较得到的差异性表达基因功能分属于细胞过程、生理过程、细胞成分、生物调节、信号转导等;有统计学意义的差异性基因通路主要有:凋亡通路、细胞周期通路、P53蛋白信号通路、Fas 信号通路、一氧化氮通路、凋亡级联通路、局部黏附通路、细胞外基质受体相互作用通路、紧密连接通路、黏着接合通路、肌动蛋白细胞骨架调节通路、骨重塑通路、硫酸软骨素生物合成通路、Jak-STAT信号通路、Wnt信号通路、Toll样受体信号通路、细胞间黏附信号通路、T细胞受体信号通路等(P＜0.05);骨关节炎.创伤组和骨关节炎-RA组之间差异性基因功能及通路存在差异,同时也存在交叉.结论 从差异性基因表达种数、生物学功能、通路分析三方面获得骨关节炎生物学信息,使得从基因表达人手寻找骨关节炎的早期预警指标成为可能.     

白藜芦醇对实验性兔骨关节炎软骨细胞凋亡及bcl-2 bax表达的影响

目的 研究白藜芦醇对兔实验性骨关节炎(OA)软骨细胞凋亡及凋亡调控基因bcl-2、bax表达的影响,探讨其治疗OA的机制.方法 30只新西兰大白兔随机平分为5组,A组(健康对照组)、B组(模型对照组)、C组(白藜芦醇高剂量干预组)、D组(白藜芦醇中剂量干预组)、E组(白藜芦醇低剂量干预组).除A组外,其他各组均以Hulth法复制膝OA模型.术后第4周开始,A组、B组每天以5 ml含0.1%二甲基亚砜的蒸馏水灌胃;白藜芦醇干预各组每天以相应剂量白藜芦醇溶液(浓度为60 mg/ml)灌胃,C、D、E组日剂量分别为120、60、30mg·kg-1·d-1,连续6周.第10周处死大白兔,取右膝关节股骨内髁内侧软骨,软骨组织切片用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法观察软骨细胞凋亡,免疫组织化学法观察软骨细胞bcl-2和bax的表达.结果 ①模型对照组关节软骨细胞凋亡率明显高于健康对照组;白藜芦醇干预各组可不同程度地降低OA软骨细胞凋亡率,差异有统计学意义(P＜0.05),且呈剂量依赖性.②与健康对照组相比,模型对照组关节软骨细胞bcl-2和bax阳性率均升高(P＜0.01),bcl-2/bax的比值降低;白藜芦醇干预后,bcl-2阳性率升高更为明显(P＜0.01);而bax阳性率有不同程度降低(P＜0.01);bcl-2/bax的比值均不同程度提高(P＜0.01).结论 白藜芦醇通过上调bcl-2的表达,下调bax的表达,提高bcl-2/bax的比值,以抑制兔实验性OA中软骨细胞的过度凋亡,达到保护软骨,防治OA的目的 .     

虾青素对脂多糖诱导小鼠急性肺损伤的保护作用

目的 研究虾青素对脂多糖(LPS)所致急性肺损伤(ALI)小鼠的保护作用.方法 雄性昆明种小鼠60只,随机分为正常对照组、急性肺损伤模型组、地塞米松阳性对照组(5 mg/kg)以及虾青素低、中、高剂量组(10、15、20 mg/kg)共6组.不同剂量虾青素给大鼠连续灌胃30 d后,腹腔注射脂多糖6.0 mg/kg建立ALI模型.在注射后6 h,收集腹主动脉血并进行左侧支气管肺泡原位灌洗以收集灌洗液,测定血中淋巴细胞亚群(CD+3、CD+4、CD+8)、肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)及丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;测定各组的肺湿重/干重比、肺组织中性粒细胞髓过氧化物酶(MPO)含量及肺组织匀浆TNF-α、白细胞介素10(IL-10)含量.结果 虾青素各剂量组均能降低因LPS诱发的血TNF-α、IL-8、MPO、MDA含量与肺组织湿重/干重比的升高,同时抑制肺组织IL-10含量、血SOD与GSH-Px活性的降低,改善血中淋巴细胞亚群分布.结论 虾青素对LPS所致ALI具有预防性保护作用.     

绿原酸对膝骨关节炎大鼠软骨细胞炎性凋亡及免疫反应的影响

目的 探讨绿原酸(CA)对膝骨关节炎(KOA)大鼠软骨细胞炎性凋亡及免疫反应的影响。方法 采用改良伸直位固定法建立KOA大鼠模型,模型成功大鼠随机分为模型组、CA低剂量(CA-L,5 mg/kg)组、CA中剂量(CA-M,10 mg/kg)组、CA高剂量(CA-H,15 mg/kg)组、塞来昔布(24 mg/kg)组,每组12只,另取12只SD大鼠(不做处理)设为对照组。以药物分组处理后,测定各组膝关节宽度、被动活动度;番红O-固绿染色检测关节软骨病理损伤情况,并进行Mankin评分;TUNEL染色检测各组膝关节软骨细胞凋亡情况;酶联免疫吸附试验(ELISA)检测各组血清免疫因子干扰素(IFN)-γ、白细胞介素(IL)-6、IL-10及转化生长因子(TGF)-β水平;Western印迹检测各组膝关节软骨细胞凋亡相关蛋白B细胞淋巴瘤(Bcl)-2、Bcl-2相关X蛋白(Bax)表达。结果 与对照组相比,模型组膝关节宽度、Mankin评分、膝关节软骨细胞凋亡率、血清IFN-γ及IL-6水平、膝关节软骨组织Bax表达明显升高(P<0.05),膝关节被动活动度、膝关节软骨组织Bcl-2表...     

虾青素对Aβ25～35诱导小鼠皮层神经元损伤的保护作用

目的 研究虾青素(AST)对Aβ25 ～35诱导小鼠皮层神经元损伤的保护作用.方法原代培养的小鼠皮层神经元用AST预孵育2h,再与老化的10 μmol/L Aβ25-35共孵育24h.采用MTT法测定细胞活力,Hoechst 33342染色观察细胞凋亡,DCFH-DA荧光法检测细胞内ROS水平,Rhodamine 123荧光法检测线粒体膜电位.结果 500～4 000 nmol/L的AST预处理能有效抑制10 μmol/L Aβ25～35诱导的神经元活力下降,降低细胞内ROS的水平.2 000 nmol/L AST对神经元线粒体膜电位的保护作用最明显,能显著抑制神经元凋亡.结论AST对Aβ25～35诱导小鼠皮层神经元损伤有明显的保护作用,其机制可能和保护线粒体功能有关.     

虾青素对异丙肾上腺素诱导的大鼠心肌纤维化的影响

目的 探讨虾青素对异丙肾上腺素（ISO）诱导的大鼠心肌纤维化的影响。方法 SD大鼠腹腔注射异丙肾上腺素（5mg/kg/d），连续注射14d，建立心肌纤维化模型，从造模第二天开始给予虾青素（5mg/kg/d和10mg/kg/d）灌胃，连续21天。实验结束后超声心动图检测大鼠心脏功能，计算心脏指数，Masson染色观察心肌纤维化水平，Western blotting 方法检测心肌胶原Ⅲ、转化生长因子-β1（TGF-β1）蛋白的表达。结果 与正常对照组比较，模型组左心室射血分数（EF）和左心室短轴缩短分数（FS）明显降低（P<0.05）,心脏指数增加，心肌纤维化明显，胶原蛋白Ⅲ及TGF-β1表达水平增加（P<0.05）；与模型组比较，低剂量虾青素组和高剂量虾青素组EF和FS明显升高（P<0.05），心脏指数减低（P<0.05），心肌纤维化程度减低，心肌胶原蛋白Ⅲ、TGF-β1表达水平明显降低（P<0.05）。 结论 虾青素能够降低异丙肾上腺素诱导的心肌纤维化水平，改善心功能。     

Astaxanthin ameliorates cartilage damage in experimental osteoarthritis

Abstract

Purpose. Astaxanthin is a red-pigment carotenoid found in certain marine animals and plants. Astaxanthin has been shown to inhibit matrix metalloproteinases (MMPs) expression in vitro. However, the effect of astaxanthin on cartilage is still unclear. The aim of this study was to investigate the effects of astaxanthin on cartilage in experimental osteoarthritis (OA).

Methods. New Zealand rabbits underwent anterior cruciate ligament transection to induce OA in right knee. Rabbits received intra-articular injection containing 0.3 ml of vehicle (dimethyl sulfoxide) or astaxanthin (50 μM). Injection was started on the day of operation, and the injection were performed once weekly for six consecutive weeks. Then, rabbits were sacrificed and the right knees were harvested for study.

Results. Cartilage degradation was reduced by astaxanthin, as assessed by morphological and histological examination. Astaxanthin inhibited the gene expression of MMP-1, MMP-3, and MMP-13 in cartilage as compared with the vehicle group.

Conclusions. The results suggest that astaxanthin may be considered as pharmaceutical agent in OA treatment.     

超氧化物歧化酶抗氧化损伤与动脉粥样硬化关系研究进展

动脉粥样硬化(AS)是心脑血管疾病的主要病理学基础,由多因素诱导的复杂病变。在其众多的致病因素中,氧化损伤与AS的发生发展密切相关。因此针对AS氧化损伤途径进行抗氧化被认为是有效预防和治疗AS的方法之一。在抗氧化酶家族中,超氧化物歧化酶(SOD)在抗氧化损伤方面发挥着重要的作用,本文对近年来SOD抗氧化损伤与AS之间关系的研究作一综述。     

Joint cartilage differentiation and osteoarthritis

During skeletal development, the mechanisms of formation, differentiation and maturation of the cartilage are important steps in the skeleton morphogenesis; these mechanisms regulate growth of long bones and joint formation. Although cartilage in the growth plate and articular cartilage are very similar, they have some differences in the differentiation mechanisms. Growth plate cartilage regulates the growth of long bones by cartilage substitution of bone, while articular cartilage is maintained by delay of chondrocyte maturation and hypertrophy. Maybe, the mechanism of cartilage maturation is activated and increased during osteoarthritis, resulting in loss of the biomechanical properties required by the joints to resist the impact required by the skeleton to move.     

软骨寡聚基质蛋白对骨关节炎软骨破坏早期诊断价值的研究

目的 探讨软骨寡聚基质蛋白(COMP)对骨关节炎软骨破坏早期诊断价值.方法 兔右后膝伸直位石膏管型固定法制作骨关节炎模型;形态学方法观察造模不同时期关节病理切片;免疫组织化学方法检测软骨内COMP水平;酶联免疫吸附试验(ELISA)方法检测血清COMP水平.应用t检验,Pearson相关性分析.结果 ①伸直位石膏管型制动2周,模型关节呈现早期骨关节炎改变,制动6周呈现典型的中晚期骨关节炎特征;②造模前、模型2周、模型6周血清COMP含量分别是[(3.35±0.20)、(3.64±0.18)、(3.96±0.44)μg/L,P均＜0.05];③未造模、模型2周、模型6周关节软骨内COMP表达强度分别是[(2.7±1.8)%,(5.7±0.7)%,(7.6±0.7)%,P均＜0.05];④模型2周血清COMP水平与模型2周组、模型6周组OA病理评分存在线性相关关系(r均＞0.770,P均＜0.05).结论 骨关节炎血清COMP检测对早期诊断骨关节炎软骨破坏具有重要的意义.

Abstract：

Objective To study the diagnostic value of cartilage oligomeric matrix protein for early cartilage destruction in osteoarthritis and assess its value in the prediction of the disease progression.Methods The osteoarthritis animal models were developed by immobilizing the right knees of 18 rabbits in full extension position using plaster East.Knee joint pathological changes at week 2 and 6 were examined for pathological severity evaluation of osteoarthritis.ELISA sandwich method was used to measure the levels of cartilage oligomeric matrix protein(COMP) in serum before and after modeling(at week 2 and 6 respectively) and immunohistolgy method was used to examine the levels of COMP in knee articular cartilage of osteoarthritis animal models.Correlation analysis was performed to demonstrate the relationship between the levels of COMP in the serum and the pathological severity of osteoarthritis.Pearson's test and t-test were used for correlation analysis.Results ①) Osteoarthritis animal models could be successfully developed by immobilizing the right knees of rabbits in full extension position using plaster east for 2 weeks.Early histopathological changes in the articular cartilage could be observed,At week 6,the typical histopathological characteristics could be seen.②With the extension of modeling time,serum COMP levels persistently increased.The serum COMP levels before modeling,at modeling week 2,week 6 were (3.35±0.20),(3.64±0.18),(3.96±0.44) μg/L respectively,the difference was significant (P＜0.05).③ The level of COMP in the articular cartilage of non-osteoarthritis animal models,models at week 2,week 6 were (2.7±1.8 )％ ,(5.7±0.7)％,(7.6±0.7)％ respectively (P＜0.05 for all).④ The level of COMP in the serum was linearily correlated with the pathological severity of osteoarthritis(r＞0.770 for all,and P＜0.05 for all).Conclusion Levels of COMP in the serum can help to make early diagnosis of osteoarthritis,and elevated COMP level can predict the progression of osteoarthritis.     

Effects of estrogen on cartilage and experimentally induced osteoarthritis

Estradiol valerate did not ameliorate experimentally induced osteoarthritis in the rabbit. Both normal and osteoarthritic cartilage were susceptible to estradiol suppression of proteoglycan synthesis. Proteoglycan concentration was not diminished with estradiol, suggesting estradiol suppression of proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased proteoglycan synthesis in the estrogen treated animals. Osteophyte proteoglycan metabolism differed from other osteoarthritic lesions. Differences in the metabolism of femoral and tibial articular cartilage were observed.     

The effects of bone turnover rate on subchondral trabecular bone structure and cartilage damage in the osteoarthritis rat model

The effects of bone turnover rate on subchondral trabecular changes and cartilage destruction were evaluated in an iodoacetate-induced osteoarthritis rat model. Thirty female rats were randomly divided into three groups as the ovariectomized group, the no-treatment group and the bisphosphonate medication group. Arthritis was induced by a single intra-articular iodoacetate injection into the right tibiofemoral joint. Eight weeks after this injection, tibiofemoral joints on both sides were scanned with a micro-CT. Subchondral trabecular indices were measured on both sides of the tibial lateral condyle epiphysis. In the ovariectomized group, the percentage of bone volume, trabecular thickness and trabecular bone pattern factor of the arthritic sides were lower than those of the control sides, while trabecular separation and structure model index of the arthritic sides were higher than those of the control sides (p < 0.05). In the no-treatment group, only trabecular thickness of the arthritic sides was lower than in the control sides (p < 0.05). In the bisphosphonate medication group, trabecular indices were no different between the arthritic and control sides. Articular cartilage destruction and severity of arthritis increased significantly in the order: ovariectomized group < no-treatment group < bisphosphonate medication group (p < 0.05). After osteoarthritis development, severities of subchondral trabecular changes appeared to be strongly affected by bone turnover rate. Furthermore, a correlation was found between cartilage destruction severity and subchondral trabecular change in the intra-articular iodoacetate-injected osteoarthritis rat model.     

虾青素胶囊治疗膝关节骨性关节炎疗效观察

目的观察虾青素胶囊治疗膝关节骨性关节炎的疗效。方法将60例膝关节骨性关节炎患者随机分为治疗组(30例)和对照组(30例)。治疗组给予虾青素胶囊治疗,对照组给予芬必得治疗。比较两组治疗前后膝关节功能评分,观察主要症状缓解情况和治疗效果。结果 (1)治疗组的疼痛缓解持续时间较对照组缩短,而疼痛缓解时间较对照组延长(P均0.01);(2)两组治疗后关节功能较治疗前均有提高(P均0.01),而治疗组比对照组更优(P0.05);(3)总有效率治疗组为66.67%,对照组为83.33%,两组疗效比较差异无统计学意义(P0.05)。结论虾青素胶囊治疗骨性关节炎有一定的疗效。