重组人内抑素对佐剂性关节炎大鼠关节软骨酸敏感离子通道的影响及其保护作用

目的观察重组人内抑素(rh-End)对佐剂性关节炎大鼠关节软骨酸敏感离子通道(ASICs)表达的影响,探讨其对关节软骨的作用。方法将大鼠随机分成正常组、AA模型组、rh-End 1.25、2.5、5.0mg·kg-1组和阿司匹林50mg·kg-1阳性对照组。弗氏完全佐剂(CFA)致佐剂性关节炎(adjuvant-induced arthritis,AA)后d10,大鼠出现继发性炎症,此时皮下注射重组人内抑素,连续7d,对照组灌胃给阿司匹林;正常组与模型组给予等容量的无菌注射用水。光学显微镜观察关节病理变化,半定量RT-PCR方法检测rh-End对AA大鼠关节软骨ASICs和蛋白聚糖体mRNA的影响,Western blot方法检测rh-End对AA大鼠关节软骨ASICs蛋白的影响,免疫组织化学技术测定rh-End对AA大鼠关节软骨中的Ⅱ型胶原蛋白合成的影响。结果rh-End各剂量组能明显抑制AA大鼠关节软骨组织中的ASICs表达,并升高关节软骨基质成分Ⅱ型胶原蛋白和蛋白聚糖体mRNA表达量。结论重组人内抑素通过抑制ASICs的表达进而保护AA大鼠关节软骨。

Recombinant human endostatin′s effect on acid sensing ion channel articular cartilage in rats with adiuvant induced arthritis and its protective function

Aim To explore the possible role of rh-End on rheumatoid arthritis(RA).Methods The rats were randomly divided into normal group,model group,rh-End 1.25,2.5,5.0 mg·kg-1 group,and control group.Adjuvant arthritis rat model was induced by a single intradermal injection of 100 μl of Freund′s complete adjuvant(CFA) on d 10.The secondary inflammation of adjuvant-induced arthritis(AA) rats appeared on the d 10 after the infection of CFA.Recombinant human endostatin(rh-End 1.25,2.5,5.0 mg·kg-1) were given for 7 days consecutively.Aspirin(50 mg·kg-1) was given as the control.Quantitative RT-PCR was used to detect ASICs and aggrecan mRNA expression in rat articular cartilage.Western blot analyses were used to detect ASICs protein expression in rat articular cartilage.The expression of typeⅡ collagen was measured by immunohistochemical method.Results rh-End significantly decreased the expression of ASICs,increased the expression of typeⅡ collagen protein and aggrecan mRNA in AA rats.Conclusion rh-End might play a protective role in articular cartilage in RA by inhibiting expression of ASICs in articular cartilage.