低聚原花青素通过介导Wnt/β-catenin信号通路对糖尿病肾病大鼠肾功能的保护作用研究

目的研究低聚原花青素通过介导Wnt/β-catenin信号通路对糖尿病肾病(DN)大鼠肾功能的保护作用。方法选择60只SD雄性大鼠,随机分为正常对照组(NC组)、DN模型组(DN组)、DN模型+不同剂量低聚原花青素组(低、中、高剂量组),采用单次腹腔注射链脲佐菌素复制DN模型,低、中、高剂量组分别给予50 mg/kg、100 mg/kg、150 mg/kg低聚原花青素灌胃,NC组和DN组给予等体积蒸馏水灌胃。分别于第4周、8周、12周、16周,检测各组大鼠24 h尿蛋白定量;16周末检测大鼠血糖、血肌酐(Scr)、尿素氮(BUN)水平;处死大鼠,取肾脏组织行苏木精-伊红及过碘酸希夫染色,观察肾组织形态学变化;检测肾组织匀浆上清液中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;实时荧光定量聚合酶链反应和Western blotting检测肾组织Wnt4、β-catenin mRNA和蛋白的表达。结果DN组血糖、Scr、BUN水平较NC组升高(P<0.05);低、中、高剂量组血糖、Scr、BUN水平较DN组降低(P<0.05)。各组大鼠灌胃4周、8周、12周、16周的24 h尿蛋白定量比较,采用重复测量设计的方差分析,结果:(1)不同时间点24 h尿蛋白定量有差异(F=102.38,P=0.000);(2)各组24 h尿蛋白定量有差异(F=86.58,P=0.000)。(3)各组24 h尿蛋白定量变化趋势有差异(F=174.64,P=0.000)。DN组大鼠肾组织活检可见肾小管萎缩、小管间质区基质增厚、纤维化等病理改变。DN组左肾指数较NC组升高(P<0.05);低、中、高剂量组左肾指数较DN组下降(P<0.05)。各组大鼠SOD活性比较,差异无统计学意义(P>0.05);与NC组比较,DN组MDA含量升高(P<0.05),与DN组比较,不同剂量组MDA含量降低(P<0.05)。DN组大鼠肾组织Wnt4、β-catenin mRNA和蛋白相对表达量高于NC组(P<0.05),不同剂量组Wnt4、β-catenin mRNA和蛋白相对表达量低于DN组(P<0.05)。结论低聚原花青素能有效降低DN大鼠24 h尿蛋白定量,减轻肾脏病理损害。低聚原花青素可能通过抗氧化作用及抑制Wnt/β-catenin信号通路,发挥肾脏保护作用。

Prognostic value of red cell distribution width in elderly patients undergoing maintenance hemodialysis

Objective:To investigate the predictive value of red blood cell distribution width(RDW)for all-cause mortality in elderly patients undergoing maintenance hemodialysis(MHD).Methods:We retrospectively analyzed the data of 172 elderly patients who initiated maintenance hemodialysis from June 2013 to June 2018.Basic data on demographic,dialysis,laboratory data and clinic outcomes were recorded.Compare the basic information of death and survival groups,such as general characteristics baseline laboratory data,baseline RDW and time average RDW during the follow-up;Cox regression analysis was used to analyze the risk factors of all-cause mortality,and predictive value of RDW for all-cause death in elderly maintenance hemodialysis patients.Results:A total of 172 elderly MHD patients were inrolled in this study with age of(66.3±6.1)years old and the dialysis duration of(27.3±15.3)months,including 94 males(54.6%).37 patients died during the follow-up period.Non-survivors had higher levels of RDW at baseline,higher time-average RDW,higher blood PTH,higher blood C-reactive protein(CRP),higher blood brain natriuretic peptide(BNP)(P<0.05)and lower albumin(P<0.05).Multivariate Cox regression analysis suggested that RDW,serum albumin,serum CRP,and serum BNP were independent risk factors for all-cause mortality in elderly patients with MHD.The receiver operating characteristic curve(ROC)showed that RDW=14.75%was the best cut-off point for predicting all-cause mortality in elderly patients undergoing MHD(P<0.01).Conclusions:High RDW is an independent risk factor for all-cause mortality in elderly patients with MHD,and it has important value for prognosis.