title: Renoprotective effects of berberine through regulation of the MMPs/TIMPs system in streptozocin-induced diabetic nephropathy in rats.
abstract: Berberine has proven protective effects on diabetic nephropathy, but the mechanism for its effects has not been comprehensively established. Hence, we aimed to explore the renoprotective mechanism of berberine on the accumulation of extracellular matrix, alterations of its major components and corresponding changes in the regulatory system, including the matrix metalloproteinases/tissue inhibitor of matrix metalloproteinases (MMPs/TIMPs) system, in diabetic nephropathy rats. In the experiments, diabetic nephropathy rats were treated with berberine (0, 50, 100, 200 mg/kg) respectively. The protein levels of transforming growth factor-β1 were then detected by Western blot, while fibronectin and type IV collagen levels were assessed using immunohistochemistry. Changes in the MMP2/9 and TIMP1/2 levels were detected using two forms simultaneously. In addition, we also measured the characteristics and biochemical indicators of the diabetic nephropathy rats. The results showed that berberine could ameliorate the fasting blood glucose, and the majority of biochemical and renal function parameters, but did not have an effect on body weight. Immunohistochemistry and Western blot examination revealed a significant increase in the MMP9 and TIMP1/2 levels, with an obvious decrease in MMP2 expression in the diabetic nephropathy rats. Berberine (100 and 200 mg/kg) could significantly improve the abnormal changes in the MMPs/TIMPs system. Meanwhile, reductions in the transforming growth factor-β1, fibronectin and type IV collagen expression levels were observed in the berberine treatment groups. Therefore, the renoprotective effects of berberine on diabetic nephropathy might be associated with changes in the extracellular matrix through the regulation of the MMPs/TIMPs system in the rat kidney.
authors.affiliation: Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province, People's Republic of China. Electronic address: jayni1990@126.com.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Ni
authors.affiliation: Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province, People's Republic of China. Electronic address: dhh728@163.com.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Ding
authors.affiliation: Anhui Provincial Cancer Hospital, Hefei, Anhui Province, People's Republic of China. Electronic address: 18326689075@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province, People's Republic of China. Electronic address: qiuyuanye1201@163.com.
authors.forename: Yuan-Ye
authors.initials: YY
authors.lastname: Qiu
authors.affiliation: Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province, People's Republic of China. Electronic address: tulcyl@vip.sina.com.
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Tang
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D024141:Collagen Type IV / Q000378:metabolism; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D024141:Collagen Type IV; D005353:Fibronectins; C576839:TIMP1 protein, rat; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D001599:Berberine; D019716:Tissue Inhibitor of Metalloproteinase-2; D013311:Streptozocin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Berberine; Diabetic nephropathy; ECM; MMPs/TIMPs system; Renal fibrosis