摘要
目的观察血管紧张素Ⅱ受体拮抗剂(ARB)缬沙坦对慢性病毒性心肌炎(VMC)小鼠Th17与CD4+CD25+Treg细胞的平衡状态及心肌病变的影响,探讨ARB对慢性VMC的作用及其机制。方法以柯萨奇病毒(CVB3)重复增量感染(第1、14、28天剂量分别为0.20、0.25、0.30 mL)BABL/c组小鼠建立慢性VMC模型(n=36),对照组(n=6)同期腹腔注射等体积生理盐水。42 d将慢性VMC模型组存活小鼠随机分为慢性VMC组和缬沙坦组,干预28 d后,处死各组小鼠。处死前测量各组小鼠血压、心脏质量和体质量;脾脏中提取淋巴细胞,采用流式细胞术检测Th17和CD4+CD25+Treg细胞比例;采用Real Time-PCR法检测Foxp3和IL-17的mRNA在心肌中的表达;心肌行HE和Masson染色;心脏超声检查小鼠心脏功能。结果各组小鼠血压水平无显著性差异(P>0.05)。慢性VMC组小鼠心脏质量/体质量比(HW/BW)大于缬沙坦干预组和对照组(P<0.01),慢性VMC组小鼠脾脏中Th17细胞的比例、IL-17、病理积分明显高于缬沙坦组和对照组(P<0.01),而CD4+CD25+Treg细胞的比例、Foxp3低于缬沙坦组和对照组(P<0.05)。缬沙坦组小鼠心功能较慢性VMC组明显改善。结论病毒性心肌炎小鼠外周血中存在Th17/Treg失衡,且与心肌病变有相关性,缬沙坦可通过调节Th17/Treg平衡,减轻慢性VMC自身免疫损伤,避免向扩张型心肌病进展。
Objective To observe the effects of angiotensin receptor U blockers （ ARB ） Valsartan on the balance between Thl7 and Treg cells in chronic viral myocarditis （VMC） and explore the effects of ARB on chronic VMC and its mechanisms. Methods BALB/c mice（n = 36） were infected with CVB3 at day 1,14 and 28 to establish the chronic VMC models. The volumes of CVB3 were 0.20,0.25 and 0.30 mL. The mice in the normal control group （ n = 6） were intraperitoneally injected with equal volumes of normal saline without CVB3 at the same time. The survival mice infecteded with CVB3 were randomly divided into the chronic VMC control group and the Valsartan therapy group at day 42. The mice of the Valsartan therapy group were administered with Valsartan 10 mg/（kg . d） for 28 days. Blood pres- sure, heart weight and body weight of all the mice were measured before execution. Lymphatic cells were extractedfrom the spleen and the ratio of Thl7 and Treg cells was evaluated by flow cytometry, mRNA of IL-17A and foxp3 were tested by Real-time PCR. The severity of myocarditis was assessed by haematoxylin-eosin （HE） and Masson＇ s trichrome. Echocardiography was performed to evaluate cardiac functions of the mice. Results There was no signifi- cant difference in blood pressure level among the three groups （ P 〉 0. 05 ）. Compared with Valsartan group and normal control group, the ratio of heart weight in chronic VMC group was higher,and the percentage of CD4 Thl7 cell and the level of IL-17 in chronic VMC group were significantly up-regulated（P 〈0.01 ）, while the pencentage of CD4 ＋ CD25 Treg cell and cytokine of foxp3 was down-regulated （P 〈0.01, P 〈0.05 respectivcly）. Cardiac functions of the mice in Valsartan therapy group increased significantly. Conclusion Thl7/Treg imbalance exists in mice with chronic VMC. Valsartan can regulate Thl7/Treg imbalance to ameliorate viral myocarditis and the progression of dilated cardiomyopathy.
出处
《山东大学学报（医学版）》
CAS
北大核心
2013年第2期1-6,11,共7页
Journal of Shandong University:Health Sciences
基金
山东省优秀中青年科学家科研奖励基金(BS2009YY027)
国家自然科学基金(81070188)
