生地黄水提液调控Wnt-5a/ROR2通路对输尿管梗阻大鼠肾纤维化的影响  

Effect of Shengdihuang aqueous extract regulating Wnt-5a/ROR2 pathway on renal fibrosis in rats with ureteral obstruction

作　　者：杨雪 韩刚 余明琼 彭婧 张晶 YANG Xue;HAN Gang;YU Mingqiong;PENG Jing;ZHANG Jing(Tangshan Union Medical College Hospital,Tangshan 063000,China)

机构地区：[1]唐山市协和医院,河北唐山063000 [2]开滦总医院泌尿外科,河北唐山063000

出　　处：《陕西中医》2023年第1期24-28,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：河北医学科学研究计划项目(20221832)。

摘　　要：目的:生地黄水提液调控Wnt-5a/ROR2通路对输尿管梗阻大鼠肾纤维化的影响。方法:将90只无特定病原体级SD大鼠,随机分为对照组(n=15)、模型组(n=15)、盐酸咪哒普利组(n=15)、生地黄水提液低剂量组(n=15)、生地黄水提液中剂量组(n=15)、生地黄水提液高剂量组(n=15),除对照组外,建立大鼠输尿管梗阻模型,造模后盐酸咪哒普利组、生地黄水提液低剂量组、生地黄水提液中剂量组、生地黄水提液高剂量组分别给0.9 g/(kg·d)盐酸咪哒普利和0.8、1.6、3.2 g/(kg·d)生地黄水提液灌胃连续2周,于实验终点确定大鼠肾脏/体重比值,采用苏木精-伊红染色法、HE染色确定各组大鼠肾脏病理水平,Masson染色确定各组大鼠肾脏纤维化水平,Western blot检测确认各组大鼠纤维化生物标志蛋白CollagenⅠ、α平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)表达水平及Wnt信号通路Wnt-5a、ROR2蛋白表达水平。结果:与对照组相比,模型组大鼠肾脏/体重比值升高,肾脏组织炎性细胞浸润增加,病理损伤增加,纤维化水平上升,纤维化生物标志物CollagenⅠ、α-SMA、Vimentin表达水平升高、Wnt-5a、ROR2蛋白表达水平升高(P<0.01);与模型组相比,生地黄水提液给药各组大鼠炎性细胞浸润降低,病理损伤降低,纤维化水平下降,纤维化生物标志物CollagenⅠ、α-SMA、Vimentin表达水平降低、Wnt-5a、ROR2蛋白表达水平降低,且具有剂量依赖效应(P<0.01)。结论:生地黄水提液可以抑制大鼠肾脏纤维化发挥肾脏保护作用,其机制可能与抑制Wnt-5a/ROR2信号通路相关。Objective:To investigate the effect of Shengdihuang aqueous extract regulating Wnt-5a/ROR2 pathway on renal fibrosis in rats with ureteral obstruction.Methods:90 SPF SD rats were randomly divided into control group(n=15),model group(n=15),imidapril hydrochloride group(n=15),low dose of Shengdihuang aqueous extract(n=15),medium dose group of Shengdihuang aqueous extract(n=15)and high dose group of Shengdihuang aqueous extract(n=15).the rat model of ureteral obstruction was established except control group.After modeling,the imidapril hydrochloride group,the low dose of Shengdihuang aqueous extract,the middle dose group and the high dose group were given 0.9 g/(kg·d)imidapril hydrochloride,0.8 g/(kg·d),1.6 g/(kg·d)and 3.2 g/(kg·d)Shengdihuang aqueous extract by gavage for 2 weeks.The renal/body mass fraction of rats was determined at the end of the experiment,the renal pathological level of rats in each group was determined by HE staining,and the renal fibrosis level of rats in each group was determined by Masson staining,the expression levels of collagenⅠ,α-SMA and Vimentin,as well as Wnt signaling pathway Wnt-5a and ROR2 were confirmed by Western blot.Results:Compared with the control group,the kidney/body mass fraction,inflammatory cell infiltration,pathological injury and fibrosis level of the model group increased,and the expression levels of CollagenⅠ,α-SMA and Vimentin,Wnt-5a and ROR2 protein were increased(P<0.01).Compared with the model group,the inflammatory cell infiltration,pathological injury,fibrosis level and the expression levels of CollagenⅠ,α-SMA and Vimentin,Wnt-5a and ROR2 protein were decreased and had a dose-dependent effect(P<0.01).Conclusion:Shengdihuang aqueous extract can inhibit renal fibrosis and exert renal protection in rats,and its mechanism may be related to the inhibition of Wnt-5a/ROR2 signal pathway.

关 键 词：输尿管梗阻 生地黄水提液 肾脏 纤维化 大鼠 

分 类 号：R693.2[医药卫生—泌尿科学]