山东医药2018，Vol.57Issue(7)：18-22,5.DOI:10.3969/j.issn.1002-266X.2018.07.005
α-乳香酸灌胃对小鼠肾间质纤维化的防治作用及其机制探讨
Preventive and therapeutic effects of α-boswellic acid on renal interstitial fibrosis in mice
摘要
Abstract
Objective To investigate the preventive and therapeutic effects of α-boswellic acid on renal interstitial fi-brosis in mice and its mechanism.Methods A total of 52 male C57/BL mice were divided into three groups: sham group,model group,and boswellic acid group.The unilateral ureter separation was performed in mice of the sham group, and mice in the other two groups underwent unilateral ureteral obstruction(UUO)to induce renal interstitial fibrosis.The mice in the boswellic acid group were administered orally 60 mg/kg α-boswellic acid after surgery for 21 days.The blood and kidney tissues in each mouse were collected after anesthesia.The levels of urea nitrogen(BUN), creatinine(Scr), malondialdehyde(MDA),and total superoxide dismutase(t-SOD)in serum were detected.The pathological changes of kidney were observed by HE and MASSON staining.Western blotting was used to detect the protein expression of α-SMA, TGF-β1,Smad2/3,and Smad7 in the renal tissues.qPCR was used to detect the mRNA expression of α-SMA,TGF-β1, Smad2/3,and Smad7 in the renal tissues.HK-2 cells were cultured and then were divided into the control group,the ex-perimental group 1 and experimental group 2.Cells in the group 1 and group 2 were cultured under hypoxia condition for 48 h to make the cell models of renal interstitial fibrosis.Before hypoxia treatment,25 μg/mL α-boswellic acid was added in the group 2.Western blotting was used to detect the protein expression of α-SMA,TGF-β1,Smad2/3,and Smad7 in each group at 48 h after culturing.Results The levels of serum BUN, Scr, and MDA in the model group were higher than those of the sham group,and the level of SOD was lower than that of the sham group(all P<0.01).The levels of serum BUN,Scr,and MDA in the boswellic acid group were lower than those of the sham group,and the level of SOD was higher than that of the model group(all P<0.05).The pathological changes indicated that the pathological injuries and degree of renal tubulointerstitial fibrosis in the boswellic acid group significantly relieved as compared with that of the model group. The mRNA and protein expression levels of TGF-β1,Smad2,Smad3,α-SMA in the kidney tissues of the model group were higher than those of the sham group, and the mRNA and protein expression of Smad 7 was lower than that of the sham group;the mRNA and protein expression levels of TGF-β1,Smad2,Smad3,and α-SMA in the boswellic acid group were lower than those of the model group, and the mRNA and protein expression of Smad 7 was higher than that of the model group(all P<0.05).The relative expression of TGF-β1,Smad2,Smad3,and α-SMA in the group 1 was higher than that of the control group,and the relative expression of Smad7 was lower than that of the control group;the relative expression of TGF-β1,Smad2,Smad3,and α-SMA in the group 2 was lower than that of the group 1,and the relative expression of Smad7 was higher than that of the group 1(all P<0.05).Conclusion The α-boswellic acid has preventive and thera-peutic effects on the renal interstitial fi-brosis in mice,and the mechanism may be involved in the down-regulation of TGF-β1,Smad2,Smad3,α-SMA,and the up-regulation of Smad7.关键词
肾纤维化/α-乳香酸/人肾小管上皮细胞/TGF-β/Smad通路Key words
renal fibrosis/α-boswellic acid/human renal tubular epithelial cells/TGF-β/Smad pathway分类
医药卫生引用本文复制引用
柳敏娜,刘天龙,刘利敏,杨振,段梦露,孙世仁..α-乳香酸灌胃对小鼠肾间质纤维化的防治作用及其机制探讨[J].山东医药,2018,57(7):18-22,5.基金项目
国家自然科学基金资助项目(81670655). （81670655）
