Fn14在自发性高血压大鼠心肌纤维化中的作用及培哚普利的干预研究

Role of Fn14 in myocardial fibrosis in spontaneous hypertension rats and the intervenient role of perindopril

目的探讨成纤维细胞生长因子诱-导早期反应蛋白14(Fn14)在自发性高血压大鼠心肌纤维化中的作用及培哚普利的干预结果。方法18只6周龄雄性自发性高血压大鼠(SHR)随机分为高血压组(SHR-C组)和培哚普利组(SHR-P组),每组9只;另取9只同龄雄性Wistar Kyoto大鼠作为正常组(WKY组),SHR-P组给予培哚普利治疗24周。实验前后测量室间隔及左室后壁背向散射积分平均强度(AII)、校正的声学强度(CAI)与峰峰强度(PPI)等超声心动图指标。24周后,处死大鼠,测量心脏重量指数(HWI),masson染色检测胶原的表达,免疫组化法检测Fn14的表达。结果30周龄时,与WKY组相比,SHR-C组HWI显著升高、Fn14表达增高(P均<0.01),室间隔及左室后壁AII、CAI明显增大(P均<0.01),PPI明显减小(P<0.01);与SHR-C组相比,SHR-P组HWI显著降低、Fn14表达降低(P均<0.01),室间隔及左室后壁AII、CAI减小(P<0.05),PPI增大(P<0.05)。Fn14表达量与胶原纤维的量呈正相关(r=0.954,P<0.01)。结论Fn14可能参与SHR心肌纤维化,培哚普利可能通过抑制其表达来减轻心肌纤维化。

Objective To investigate the expression of fibroblast growth factor-inducible 14 （ Fnl4 ） and the effects of perindopril on it in spontaneous hypertension rats（SHR）. Methods 8 six-week-old male SHR were randomly divided into two groups ： the SHR group（ SHR-C, n = 9 ） and the perindopril group （ SHR-P, n = 9 ）. Another 9 six-week-old male Wistar Kyoto rats were recruited as the healthy control （WKY）. Rats in the SHR-P group were treated with perin- dopril for 24 weeks. An echocardiographic scan was performed in each group to measure the average image intensity （All）, peak to peak intensity （PPI） and corrected acoustic intensity （CAI） at the inter-ventricular septum and left ventricular lateral wall at the beginning and end of the experiment. After 24 weeks, all rats were killed. The heart weight was measured to calculate the heart weight index（HWI） ,the total collagen was studied by Masson staining and expression of Fnl4 was evaluated by immunohistochemical technique. Results HWI and expression of fnl4 in the SHR-C group rats were significantly increased（P 〈 0. 01 ）compared with the WKY group; HWI and expression of fnl4 in SHR-P group rats were remarkably decreased in comparison with the SHR-C group（P 〈 0. 01 ）. Compared with the WKY group, AII and CAI at the inter-ventricular septum and left ventricular lateral wall in SHR-C group rats were sig- nificantly increased（ P 〈 0. 01 ）, while PPI was significantly decreased （ P 〈 0. 01 ） ;AII and CAI in SHR-P group rats were decreased while PPI was increased compared with the SHR-C group（ P 〈 0. 05 ）. Expression of Fnl4 correlated well with collagen fibers （ r = 0. 954,P 〈 0.01 ）. Conclusions Fnl4 may play a role in myocardial fibrosis. Perindopril may ameliorate myocardial fibrosis through decreasing expression of Fnl4.