基于Shh/Gli1信号通路探讨肾衰宁颗粒对5/6肾切除肾衰竭模型大鼠肾间质纤维化的影响  

Exploring the Effect of Shh/Gli1 Signaling Pathway on Renal Interstitial Fibrosis in a 5/6 Nephrectomy Model of Nephrosis in Rats

作　　者：兰欣蓉 卫雅妮 范国荣 魏丽娟 邹文娟 杨洪涛[1] LAN Xinrong;WEI Yani;FAN Guorong(The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,300382)

机构地区：[1]天津中医药大学第一附属医院,天津300382 [2]国家中医针灸临床医学研究中心,天津300382 [3]江西省进贤县人民医院,进贤331700

出　　处：《中国中西医结合肾病杂志》2023年第8期674-678,I0003,共6页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的:研究肾衰宁颗粒抑制Shh/Gli1信号通路改善5/6肾切除肾衰模型大鼠肾间质纤维化的作用机制。方法:将40只大鼠随机分为假手术组、模型组、肾衰宁颗粒低、中、高剂量组(0.675、1.35、2.7 g/kg),每组8只。除假手术组外其余各组大鼠均通过5/6肾切除术建立慢性肾衰竭模型。术后,给药组大鼠每日灌胃相应药物,假手术组和模型组大鼠灌胃等体积生理盐水,连续12周。检测大鼠血清中Scr、BUN、Alb、TG、TC、AST、ALT水平,以及TGF-β、ColⅠ的含量;HE染色和Masson染色观察大鼠肾脏组织形态和纤维化情况;Western Blot法检测大鼠肾脏组织中Shh、Gli1、α-SMA、ColⅠ、FN蛋白的表达水平。结果:与假手术组比较,模型组大鼠血清中Scr、BUN、TG、TC水平,TGF-β、ColⅠ含量,肾脏组织中Shh、Gli1、α-SMA、ColⅠ、FN蛋白的表达水平均明显升高(P<0.05),血清中Alb含量明显降低(P<0.05),AST、ALT含量差异无统计学意义(P>0.05);肾脏病理形态学观察显示肾小管扩张,胶原沉积明显,肾间质炎性细胞浸润明显。经肾衰宁颗粒干预后,大鼠血清、肾脏组织中上述指标水平均有不同程度的改善,肾脏组织病理损伤、胶原沉积均有所减轻。结论:肾衰宁颗粒可改善5/6肾切除肾衰模型大鼠的肾间质纤维化,其作用机制可能与抑制Shh/Gli1信号通路有关。Objective:To investigate the mechanism of inhibiting Shh/Gli1 signaling pathway in renal failure in 5/6 nephrectomy nephrectomy model rats to improve interstitial fibrosis.Methods:Forty rats were randomly divided into sham-operated group,model group and low,medium and high dose groups(0.675 g,1.35 g and 2.7 g/kg)of renal failure pellets,8 rats in each group.The chronic renal failure model was established by 5/6 nephrectomy in all the groups except the sham-operated group.After surgery,the rats in the drug administration group were given the corresponding drugs by gavage daily,and the rats in the sham-operated and model groups were given saline in equal volume by gavage for 12 weeks.The levels of Scr,BUN,Alb,TG,TCHO,AST,ALT,TGF-βand ColⅠwere measured in the serum of the rats.expression levels in rat kidney tissues.Results:Compared with the sham-operated group,the serum levels of Scr,BUN,TG and TCHO,TGF-βand ColⅠ,and the expression levels of Shh,Gli1,α-SMA,ColⅠand FN proteins in the kidney tissues of rats in the model group were significantly higher(P<0.05),the serum levels of Alb were significantly lower(P<0.05),and the levels of AST and ALT were not significantly different(P>0.05).There was no significant difference in the levels of AST and ALT(P>0.05);the morphological observation of renal pathology showed that the renal tubules were dilated,collagen deposition was obvious,and inflammatory cell infiltration in the renal interstitium was obvious.After the intervention of Renal Failure Ning granules,the levels of the above indicators in the serum and kidney tissues of the rats were improved to different degrees,and the histopathological damage and collagen deposition in the kidney were reduced.Conclusion:Renal failure granules can improve interstitial fibrosis in 5/6 nephrectomized nephrosis model rats,and its mechanism of action may be related to the inhibition of Shh/Gli1 signaling pathway.

关 键 词：肾衰宁 慢性肾衰竭 肾间质纤维化 Shh/Gli1 

分 类 号：R285.5[医药卫生—中药学]