肾靶向黄芩苷-溶菌酶结合物调控糖尿病肾病大鼠NF-κB信号通路改善肾脏纤维化作用机制探讨  

Mechanism of renal-targeted baicalin-lysozyme regulates NF-κB signaling pathway in diabetic kidney disease rats to improve renal fibrosis

作　　者：张伟[1] 陈再欢 刘双春[2] ZHANG Wei;CHEN Zaihuan;LIU Shuangchun(Taizhou Municipal Hospital,Taizhou318000,China)

机构地区：[1]台州市立医院内分泌科,浙江台州318000 [2]台州市立医院输血科,浙江台州318000

出　　处：《社区医学杂志》2023年第14期724-730,共7页Journal Of Community Medicine

基　　金：浙江省科技厅项目(LGD21H100002);浙江省中医药科技计划(2021ZB332)。

摘　　要：目的探讨肾靶向黄芩苷-溶菌酶(BAI-LZM)调控糖尿病肾病(DKD)大鼠核因子κB(NF-κB)信号通路改善肾脏纤维化的作用及可能的调控机制。方法45只雄性SD大鼠随机分为正常对照组(NC组,n=10)、DKD模型组(n=15)、BAI组(n=10)和BAI-LZM组(n=10)。正常组常规饲养,DKD组、BAI和BAI-LZM组建立DKD模型,分别给予相应制剂灌胃处理。固定时间点监测大鼠体质量、空腹血糖(FBG)和血清胰岛素水平,观察各组大鼠肾脏病理学变化,免疫荧光检测NF-κB p65表达,蛋白质印迹法检测NF-κB p65、p-p65、IL-6和IL-1β蛋白表达。结果与DKD组比较,BAI和BAI-LZM组大鼠在治疗后4和8周血糖水平明显下降。NC组大鼠胰岛素水平为(29.15±10.18)mIU/L,DKD组为(6.63±1.68)mIU/L,BAI组为(11.10±2.74)mIU/L,BAI-LZM组为(13.54±2.76)mIU/L;DKD组低于NC组,t=4.565,P<0.001;BAI组高于DKD组,t=4.495,P<0.001;BAI-LZM组高于DKD组,t=6.646,P<0.001;BAILZM组与BAI组差异无统计学意义,t=1.764,P=0.100。BAI和BAI-LZM均能改善肾脏组织病理学损伤。免疫荧光检测NF-κB p65表达,NC组为56.52±6.40,DKD组为115.41±15.90,BAI组为82.42±10.41,BAI-LZM组为76.53±18.28;DKD组高于NC组,t=5.952,P=0.004;BAI组(t=3.007,P=0.040)和BAI-LZM组(t=2.780,P=0.050)均低于DKD组。蛋白质印迹检测结果显示,与DKD组相比,BAI组(t=8.154,P=0.001)和BAI-LZM组(t=24.890,P<0.001)的p-p65/p65降低,且BAI-LZM组效果更佳,t=7.933,P=0.001;BAI组IL-1β(t=2.966,P=0.041)和IL-6(t=5.814,P=0.004)的表达水平均降低;与BAI组相比,BAI-LZM组IL-1β的表达水平降低,t=3.873,P=0.018。结论BAI和BAI-LZM均可延缓DKD的进展,改善肾脏纤维化,且BAI-LZM效果更佳。其作用机制可能与BAI-LZM调节NF-κB信号通路活性降低炎性细胞因子表达密切相关。Objective To study the effect and mechanism of nuclear factor kappa-B(NF-κB)signaling-mediated inflammatory response on renal fibrosis in baicalin-lysozyme(BAI-LZM)-induced diabetic kidney disease(DKD)rats.Methods Totally 45male SD rats were randomly divided into normal control(NC)group(n=10),DKD group(n=15),BAI group(n=10),and BAI-LZM group(n=10).NC group was fed converntionally,the rat model of DKD were constructed,and then different drug was administered by gavage respectively.Body weight,fasting blood glucose(FBG)and serum insulin levels of rats were monitored at fixed time points.The pathological changes of kidney was observed,NF-κB p65expression was detected by immunofluorescence(IF)and western blot,and the expressions of p-p65,IL-6and IL-1βprotein were detected by western blot.Results Compared with the DKD group,the BAI and BAI-LZM groups showed a significant decrease in blood glucose levels at 4and 8weeks after modeling.The insulin levels were(29.15±10.18)mIU/L in the NC group,(6.63±1.68)mIU/L in the DKD group,(11.10±2.74)mIU/L in the BAI group,and(13.54±2.76)mIU/L in the BAI-LZM group.The DKD group was lower than the NC group(t=4.565,P<0.001),the BAI group was higher than the DKD group(t=4.495,P<0.001),and the BAI-LZM group was higher than the DKD group(t=6.646,P<0.001).There was no statistically significant difference between the BAI-LZM group and the BAI group(t=1.764,P=0.100).Both BAI and BAI-LZM could improve the renal histopathology injury.The immunofluorescence test results showed that the expression of NF-κB p65was 56.52±6.4in the NC group,115.41±15.9in the DKD group,82.42±10.41in the BAI group,and 76.53±18.28in the BAI-LZM group.The DKD group was higher than the NC group(t=5.952,P=0.004),while the BAI group(t=3.007,P=0.040)and BAI-LZM group(t=2.780,P=0.050)were both lower than the DKD group.The results of western blot analysis showed that,compared with the DKD group,the BAI group(t=8.154,P=0.001)and BAI-LZM group(t=24.890,P<0.001)showed a decrease in pp65/p65,and the BAI-LZM group had

关 键 词：肾靶向 黄芩苷-溶菌酶 糖尿病肾病 NF-ΚB信号通路 纤维化 

分 类 号：R285.5[医药卫生—中药学]