Effects of dual inhibition of angiotensin Ⅱ receptor- neprilysin on oxidative stress and fibrosis in the genital tract of female spontaneous hypertensive rats

摘要

Objective: In this study, we investigated the effects of LCZ696 on oxidative stress infemale hypertensive genital tract. Methods: We used 16-week-old SPF-grade spontaneously hypertensive rats. They were randomly divided into LCZ696 group, valsartan group, diuretic group (chlorothiazone) and spontaneously hypertensive rat group (SHR group), and control group (WKY group) with 10 rats in each group. During the three-month period of administration, the drugs were given by gavage. After 12 weeks, all rats were operated on in aseptic operation, and their vaginal tissues were dissected for subsequent tests. The oxidative stress index (eNOS, nNOS protein expression) was measured by Western blot, and the degree of vaginal fibrosis was observed by HE staining. Results: (1). Changes of blood pressure in rats: Compared with the SHR group, the LCZ696, valsartan and chlorothiazone groups could significantly reduce blood pressure, including systolic blood pressure, diastolic blood pressure and mean arterial blood pressure; and the decrease of systolic blood pressure in LCZ696 group was more significant than that in valsartan and chlorothiazone group; (2). Western blotting results: Compared with spontaneously hypertensive rats, the expression of eNOS, nNOS protein in LCZ696 group and valsartan group was significantly up-regulated (P < 0.05), but there was no statistical significance in chlorothiazone group; (3). HE staining results: The results of WKY group (control group) showed that the morphology of vaginal epithelium was basically normal, collagen fibers did not increase, and arranged neatly, no obvious pathological changes occurred. In SHR group, the thickness of vaginal epithelium was significantly increased, the keratinization was obvious, collagen fibers increased significantly, and arranged disorder, pathological changes were obvious. Both LCZ696 group and valsartan group were observed the reduce of vaginal epithelial hyperplasia, the increase of collagen fibers. Additionally, LCZ696 could significantly alleviate the increase of vaginal epithelium, collagen fiber and the degree of fibrosis, compared with valsartan group. However, the effect of chlorothiazone on the reduction of vaginal fibrosis is not obvious. Conclusion: The causes of gentital tract fibrosis in spontaneously hypertensive female rats are related to oxidative stress. LCZ696 can inhibit oxidative stress and inflammation to some extent, improve vascular endothelial injury of gentital tract, reduce the degree of fibrosis, and thus ameliorate gentital tract remodeling in spontaneously hypertensive female rats.