血管紧张素Ⅱ抑制剂对炎症性关节囊粘连的影响

Effects of angiotensinⅡinhibitors on inflammatory intra-capsular adhesion

目的评价血管紧张素(Ang)Ⅱ抑制剂对大鼠炎症性关节囊粘连的影响。方法 20只Sprague-Dawley大鼠随机分为胶原诱导性关节炎(CIA)模型氯沙坦治疗组(A组)、CIA模型雷米普利治疗组(B组)、CIA模型对照组(C组)和正常对照组(D组),每组5只。实验第18、21、24、27、30天分别对大鼠四肢肢端肿胀程度进行Baggott关节炎评分,第30天测量膝关节活动度,取膝关节标本作苏木精-伊红(HE)染色观察滑膜细胞增殖情况,经免疫组化检测观察血管紧张素转化酶(ACE)、AngⅡ1型受体(AT1R)和AngⅡ在关节滑膜中表达情况。结果 A组大鼠经氯沙坦治疗,B组大鼠经雷米普利治疗后关节肿胀程度减轻,膝关节活动度由C组平均100.52°±16.74°提高至A组平均113.15°±12.19°和B组平均130.59°±6.87°,差异有显著统计学意义(P≤0.05)。HE染色显示A组和B组大鼠分别经氯沙坦和雷米普利治疗后关节成纤维样滑膜细胞增殖抑制,免疫组化检测显示ACE、AT1R和AngⅡ水平分别在氯沙坦和雷米普利干预下均降低。结论 AngⅡ抑制剂可抑制CIA模型大鼠成纤维样滑膜细胞增殖,减轻关节炎症,并改善关节囊粘连,增加膝关节活动度。

Objective To evaluate the effects of angiotensin （Ang） Ⅱinhibitors on inflammatory capsular adhesion in rats Methods Twenty Sprague-Dawley rats were randomly divided into 4 groups with 5 rats in each： collagen induced arthritis （CIA rat models with Ang receptor blocker （ARB） losartan treatment were in group A, CIA rat models with Ang-converting enzyrr inhibitor （ACEI） ramipril treatment in group 13, CIA rat models with normal saline in group C （control） and normal rats in grop D （normal control）. Paw swelling was accessed by Baggott arthritis scoring system on day 18, 21, 24, 27 and 30. Range motion （ROM） of knee joints was recorded on day 30. The pathological morphology of joint synovium and expression of Ar converting enzyme （ACE）, Ang Ⅱ type I receptor （ATIR） and Ang Ⅱ in synovium were observed by hematoxylin cosin （HE staining and immunohistoehemistry. Results Losartan and ramipril both alleviated the paw swelling, the mean ROM of knee joints increased from 100.52°± 16.74°（group C） to 113. 15 °±12. 19°（group A） and 130. 59°± 6. 87°（group B）, and statistic analysis showed the differences were significant （P≤0, 05）. HE staining and irnrnunohistochemistry examination indicated losartan and ramipril inhibited fibroblast-like synoviocyte proliferation, the expressions of ACE, AT 1R and Ang Ⅱwere down regulate〈 Conclusions Ang Ⅱ inhibitors can significantly reduce fibroblast-like synoviocyte proliferation in rats with CIA, allevia＇ inflammatory symptoms and joint capsule fibrosis, and improve ROM of involved joints.