黄芪桂枝五物汤对老年糖尿病肾病转化生长因子-β基因表达调控区甲基化的影响

李国宏 纪品川 王雅君

摘要 目的：觀察黄芪桂枝五物汤对老年糖尿病肾病（DN）的临床疗效，同时分析其对转化生长因子-β（TGF-β）基因表达调控区甲基化的影响。方法：选取2016年6月至2017年6月承德市中医院收治的老年DN患者90例，随机分成对照组和观察组，每组45例。2组患者均接受糖尿病教育、糖尿病饮食，观察组在此基础上加用黄芪桂枝五物汤，2组均以6周作为1个疗程，3个疗程后观察疗效、蛋白尿排泄率和TGF-β基因甲基化水平。结果：2组临床总有效率比较，观察组优于对照组，差异有统计学意义（P<0.05）。治疗后2组患者UAER均较治疗前改善，观察组改善的幅度更为明显（P<0.05）。治疗后2组的VEGF蛋白和mRNA表达均有所下降，其中观察组下降的趋势较对照组明显（P<0.05）。观察组TGF-β基因甲基化为（13.66±8.22）%，对照组组为（66.89±11.18）%，明显低于观察组（P<0.05）。结论：黄芪桂枝五物汤可有效治疗老年糖尿病肾病，其作用机制可能与降低TGF-β基因表达调控区甲基化水平有关。

关键词 黄芪桂枝五物汤;2型糖尿病;糖尿病肾病;老年;临床疗效;转化生长因子-β基因;甲基化;作用机制

Effects of Huangqi Guizhi Wuwu Decoction on Methylation of TGF-β Gene Expression Regulatory Region

in the Treatment of Elderly Patients with Diabetic Nephropathy

Li Guohong， Ji Jinchuan， Wang Yajun

（Chengde City Hospital of Geriatrics， Hebei 067000， China）

Abstract Objective：To observe the clinical effects of Huangqi Guizhiwuwu Decoction on senile diabetic nephropathy and to analyze its effects on methylation of TGF-β gene expression regulatory region. Methods：A total of 90 cases of elderly DN patients admitted to our department from June 2016 to June 2017 were randomly divided into control group and observation group， with 45 cases in each group. Two groups of patients were under instruction of diabetes education， and took diabetes diet. Patients in the observation group took Huangqi Guizhi Wuwu Decoction on the basis of therapeutic schedule， and all the patients were treated for 3 courses （6 weeks as a course of treatment）. After the treatment， clinical effects， proteinuria excretion rate and TGF-β gene methylation levels were observed. Results：1） The comparison of total effective rates of the two groups were statistically significant （P<0.05）， and the rate in the observation group was superior to that in the control group. 2） After treatment， the uAER of the two groups was improved compared with that before treatment， and the improvement of the observation group was more significant （P<0.05）. 3） The expressions of VEGF and mRNA in the two groups decreased after treatment， and the trend of the observation group was significantly lower than that of the control group （P<0.05）. 4） The level of methylation of TGF-β gene was （13.66±8.22）% in the observation group and （66.89±11.18）% in the control group， which was significantly lower than that in the observation group （P<0.05）. Conclusion：Huangqi Guizhi Wuwu decoction can effectively treat senile diabetic nephropathy and its mechanism may be related to reducing the level of methylation of TGF-β gene expression regulation.

Key Words Huangqi Guizhi Wuwu Decoction; Type 2 diabetes mellitus; Diabetic Nephropathy; Elderly; Clinical efficacy; TGF-β Gene; Methylation; Mechanism

中图分类号：R289.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2018.03.024

糖尿病肾病（Diabetic Nephmpathy，DN）是由遗传、代谢因素、肾脏系统血流动力学、各种细胞因子及氧化应激共同作用所导致的作为糖尿病的常见并发症之一，其临床表现常以持续性微量蛋白尿和肾小球滤过率进行性下降为主[1]。该病主要是以老年人为主，随着目前生命质量的改善及人口老龄化，老年DN发病率逐年上升，在老年性疾病中高达46%[2]。老年DN是一个缓慢发展的过程，肾功能的早期损害是可逆的，而肾功能损害是糖尿病的并发症，故如果能在糖尿病早期予以及时有效的治疗，不仅可避免肾功能损害的发生，也可延缓老年DN的恶化。

目前，在中医古籍中，并没有对对老年DN有详细描述，其认为多属于“消渴”“水肿”“胀满”“关格”等范畴，并认为其发病机制为：脏气虚衰、瘀血阻滞、水湿内停[3]。……