Exogenous pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction

查看全文 作　　者：Li-zhe [1]Jin;Hui-ying [1,2]Li;Jian [1]Jin;Shang-guo [1]Piao;Xiong-hu [3]Shen;Yan-ling [4]Wu;Jia-chong [5]Xu;Long-ye [1]Zhang;Yu-ji [1]Jiang;Hai-lan [1]Zheng;Ying-shun [1]Jin;Sheng [1]Cui;Kang [1]Luo;Yi [1]Quan;Can [1]Li

机构地区：[1]Department of Nephrology,Yanbian University Hospital,Yanji 133000,China;[2]Postdoctoral Research Institute,Yanbian University Hospital,Yanji 133000,China;[3]Department of Oncology,Yanbian University Hospital,Yanji 133000,China;[4]Department of Pharmacology,Yanbian University,Yanji 133000,China;[5]Animal Care Institute,Yanbian University,Yanji 133000,China

出　　处：《Acta Pharmacologica Sinica》索引2020年第41卷第12期,共12页

基　　金：This work was supported by the National Natural Science Foundation of China(no.81560125,no.81760293;no.81760132,and no.81760668)and the Korean Health Technology Research and Development Project,Ministry for Health and Welfare(grants HI14C3417 and HI16C1641). 摘　　要：Tissue kallikrein has protective function against various types of injury.In this study,we investigated whether exogenous pancreatic kininogenase(PK)conferred renoprotection in a rat model of unilateral ureteral obstruction(UUO)and H2O2-treated HK-2 cells in vitro.SD rats were subjected to UUO surgery,then PK(7.2 U/g per day,ip)was administered for 7 or 14 days.After the treatment,rats were euthanized;the obstructed kidneys were harvested for further examination.We found that PK administration significantly attenuated interstitial inflammation and fibrosis,and downregulated the expression of proinflammatory(MCP-1,TLR-2,and OPN)and profibrotic(TGF-β1 and CTGF)cytokines in obstructed kidney.UUO-induced oxidative stress,closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling,which were abolished by PK administration.We further showed that PK administration increased the expression of bradykinin receptors 1 and 2(B1R and B2R)mRNA and the production of NO and cAMP in kidney tissues.Coadministration with either B1R antagonist(des-Arg9-[Leu8]-bradykinin)or B2R antagonist(icatibant)abrogated the renoprotective effects of PK,and reduced the levels of NO and cAMP in obstructed kidney.In H2O2-treated HK-2 cells,addition of PK(6 pg/mL)significantly decreased ROS production,regulated the expression of oxidant and antioxidant enzymes,suppressed the expression of TGF-β1 and MCP-1,and inhibited cell apoptosis.Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys. 关键词：KALLIKREIN renal fibrosis oxidative stress APOPTOSIS AUTOPHAGY

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Exogenous pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction

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