骨形态发生蛋白-7对尿毒症大鼠肾脏的保护作用

Renoprotection of Bone Morphogenetic Protein-7 in Uremic Rats

目的:观察骨形态发生蛋白-7对尿毒症大鼠肾脏Klotho表达及氧化应激的影响,探讨其对肾损伤的保护作用机制。方法:雄性SD大鼠切除右肾并结扎左肾动脉前支诱导尿毒症模型。将20只尿毒症鼠随机分为尿毒症组(UC组)、UC+骨形态发生蛋白-7治疗组(UB组)。另设正常SD大鼠为对照组(NC组)。第12周检测大鼠血清钙(Ca)、磷(P)、成纤维细胞生长因子23(FGF23)、白蛋白、尿素氮(BUN)、血肌酐(Cr)、24h尿蛋白(24 h UP)。并检测肾脏总抗氧化能力(TAOC)、丙二醛(MDA)、铜锌超氧化物歧化酶(Cu/Zn SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平。RT-PCR检测肾组织Klotho、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1 mRNA的表达。结果:与NC组相比,UC组P、FGF23、BUN、Cr、24 h UP较NC组显著升高(P<0.01),Ca、Alb降低(P<0.05或0.01);T-AOC、Cu/zn SOD、GSH-Px显著降低(P<0.01),MDA明显升高(P<0.01);肾组织Klotho mRNA的表达显著降低,而TNF-α及MCP-1 mRNA的表达则显著升高。BMP-7改善尿毒症鼠肾病理损伤和矿物质代谢,减少尿蛋白的排泄;降低氧化应激反应,恢复Klotho的表达,抑制TNF-α、MCP-1的表达。结论:BMP-7通过上调Klotho的表达,抑制氧化应激反应而具有保护肾脏作用。

Objective：To explore the effects of bone morphogenetic protein-7（BMP-7） on renal Klotho expression and oxidative stress in uremic rats and the mechanisms underlying the protection against renal damage.Method：Uremic rats of male Sprague-Dawley were induced by the ligation of anterior branches of the left renal artery and excision of the right kidney.Uremic rats were randomly divided into two groups,uremic group（UC group） and uremic with BMP-7 treatment group（UB group）.A group of normal rats were served as the normal group（NC group）.At the 12th week,the levels of serum calcium,phosphorus,fibroblast growth factor 23 （FGF23）,albumin（Alb）,urea nitrogen（BUN）,creatinine（Cr） and 24-hour urinary protein（24 h UP） were measured.The levels of total antioxidant capacity（TAOC）,malondialdehyde（MDA）,Cu/Zn superoxide dismutase（Cu/Zn SOD） and glutathione peroxidase （GSH-Px） were determined.The renal mRNA expression of Klotho,tumor necrosis factor-α（TNF-α） and monocyte chemotactic protein-1（MCP-1） were determined by RT-PCR.Result：Compared with those in the NC group,the levels of P,FGF23,BUN,Cr and 24 h UP in serum,the content of MDA and the expression of TNF-αand MCP-1 mRNA in renal tissue were increased（P 0.01） while serum Ca,Alb,activities of TAOC,Cu/Zn SOD and GSH-Px,and renal Klotho expression were decreased（P0.05 or 0.01） in the UC group.BMP-7 could ameliorate renal pathological damage and mineral metabolism,reduce proteinuria and oxidative stress, restore the expression of Klotho and inhibit mRNA expression of TNF-αand MCP-1 in the uremic rats.Conclusion：BMP-7 can exert protection against renal damage in uremic rats through upregulating Klotho expression as well as reducing oxidative stress.