免疫抑制方案中他克莫司联合缬沙坦对慢性移植肾失功患者肾功能、脂代谢的影响及机制研究
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篇名: 免疫抑制方案中他克莫司联合缬沙坦对慢性移植肾失功患者肾功能、脂代谢的影响及机制研究
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摘要: 目的:探讨免疫抑制方案中他克莫司联合缬沙坦对慢性移植肾失功(CAD)患者肾功能、脂代谢及基质金属蛋白酶2(MMP-2)、MMP-9、基质金属蛋白酶组织抑制因子2(TIMP-2)和转化生长因子β(TGF-β)水平的影响。方法:选取2016年3月-2018年6月我院肾内科收治的CAD患者,按照随机数字表法分为A、B、C 3组,每组34例。A组患者采用环孢素A+吗替麦考酚酯胶囊+醋酸泼尼松片治疗;B组患者采用他克莫司胶囊+吗替麦考酚酯胶囊+醋酸泼尼松片治疗;C组患者在B组基础上辅以缬沙坦治疗;连续治疗3个月,比较各组患者肾功能指标[24 h尿蛋白、血肌酐(Scr)]、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)] 及MMP-2、MMP-9、TIMP-2、TGF-β水平差异。结果:治疗前,3组患者上述指标差异均无统计学意义(P>0.05)。治疗后,A组患者24 h尿蛋白、Scr、TC水平仍高于正常范围,其他脂代谢指标在正常范围内;B组患者24 h尿蛋白、TC水平仍高于正常范围,Scr水平在正常范围上限附近,其他脂代谢指标在正常范围内;C组患者肾功能指标和脂代谢指标均在正常范围内,且肾功能指标水平明显低于B组(P<0.05),脂代谢指标与B组差异无统计学意义(P>0.05)。与治疗前比较,A组患者TGF-β水平明显升高(P<0.05),MMP-2、MMP-9、TIMP-2水平差异无统计学意义(P>0.05);B组和C组患者TGF-β水平明显升高(P<0.05),MMP-2、MMP-9、TIMP-2水平明显降低(P<0.05)。结论:他克莫司联合缬沙坦能够有效延缓CAD患者肾功能减退,改善脂代谢,其机制可能与抑制MMP-2、MMP-9、TIMP-2、TGF-β表达有关。
ABSTRACT: OBJECTIVE: To investigate the effects of tacrolimus combined with valsartan in immunosuppressive regimen on renal function, lipid metabolism and matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of matrix metalloproteinases 2 (TIMP-2) and transforming growth factor-β (TGF-β) in patients with chronic allograft dysfunction (CAD). METHODS: CAD patients admitted to nephrology department of our hospital from Mar. 2016 to Jun. 2018 were enrolled in group A, B, and C according to the random number table, 34 cases in each group. Group A was given cyclosporin A+Mycophenolate capsules+Prednisone acetate tablets; group B was treated with tacrolimus+Mycophenolate capsules+Prednisone acetate tablets; group C was treated with valsartan on the basis of group B; they were treated for continuous 3 months. Renal function indexes (24 h urinary protein, Scr), lipid metabolism indicators (TC, TG, HDL, LDL) and the levels of MMP-2, MMP-9, TIMP-2 and TGF-β were compared among those groups. RESULTS: Before treatment, there was no statistical significance in above indexes among 3 groups (P>0.05). After treatment, 24 h urinary protein, Scr and TC levels of group A were still higher than normal level, while other lipid metabolism indexes were within normal range. 24 h urinary protein and TC level of group B were still higher than normal level, while Scr level was near the upper limit of the normal range, and other lipid metabolism indicators were within the normal range. Renal function indexes and lipid metabolism indexes of group C were within normal range, while renal function indexes levels of it were lower than those of group B (P<0.05); there was no statistical significance in lipid metabolism indexes, compared with group B (P>0.05). Compared with before treatment, TGF-β level of group A was significantly increased (P<0.05); there was no statistical significance in MMP-2, MMP-9 or TIMP-2 levels (P>0.05). TGF-β level of group B and group C was increased significantly (P<0.05), while the levels of MMP-2, MMP-9 and TIMP-2 were decreased significantly (P<0.05). CONCLUSIONS: Tacrolimus combined with valsartan can effectively delay renal dysfunction and improve lipid metabolism in CAD patients. The mechanism may be related to the inhibition of TIMP-2, MMP-2, MMP-9 and TGF-β expression.
期刊: 2019年第30卷第15期
作者: 刘琴,邹和群
AUTHORS: LIU Qin,ZOU Hequn
关键字: 他克莫司;缬沙坦;慢性移植肾失功;肾功能;脂代谢;机制
KEYWORDS: Tacrolimus; Valsartan; Chronic allograft dysfunction; Renal function; Lipid metabolism; Mechanism
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