缬沙坦联合氨氯地平对抗Thy1肾小球肾炎大鼠系膜增生的拮抗作用研究

Antagonistic effect of valsartan combined with amlodipine on mesangial hyperplasia in Thy1 glomerulonephritis rats

目的探究缬沙联合坦氨氯地平对抗Thy1肾小球肾炎大鼠系膜增生拮抗作用。方法大鼠经尾静脉一次性注射兔抗大鼠胸腺细胞免疫血清建立抗Thy1肾小球肾炎模型,并将建模成功的大鼠随机分为模型组、对照组、实验组和联合组,每组12只;另取12只大鼠注射等量0.9%NaCl作为正常组。对照组给予16 mg·kg^(-1)缬沙坦,实验组给予10 mg·kg^(-1)氨氯地平,联合组给予16 mg·kg^(-1)缬沙坦+10 mg·kg^(-1)氨氯地平,正常组和模型组均给予等量0.9%NaCl。5组大鼠每天灌胃给药1次,连续给药14 d。用全自动生化分析仪检测尿液中的24 h尿蛋白(24 h UP)、血尿素氮(BUN)和血清肌酸酐(SCr)含量,用蛋白质印迹法检测肾组织中p38丝裂原激活蛋白激酶/核转录因子κB(p38MAPK/NF-κB)通路蛋白的表达水平。结果联合组、实验组、对照组、模型组和正常组的24 h UP分别为(2.03±0.31)、(3.75±0.94)、(3.68±0.92)、(4.95±1.23)和(0.27±0.07)mg·d^(-1),BUN分别为(13.16±3.29)、(17.65±4.41)、(17.94±4.49)、(22.75±5.69)和(8.96±2.24)μmol·L^(-1),SCr分别为(50.15±12.53)、(62.05±15.51)、(63.13±15.78)、(83.27±20.82)和(40.15±10.03)μmol·L^(-1),p-p38MAPK/p38MAPK分别为0.51±0.13、0.70±0.17、0.72±0.18、0.99±0.25和0.21±0.05,NF-κB p65蛋白相对表达水平分别为0.55±0.14、0.79±0.20、0.81±0.21、1.12±0.28和0.18±0.05。实验组、对照组、联合组的上述指标均较模型组明显降低,差异均有统计学意义(均P<0.05);联合组的上述指标均较实验组和对照组明显降低,差异均有统计学意义(均P<0.05)。结论缬沙坦联合氨氯地平对抗Thy1肾小球肾炎大鼠系膜增生有拮抗作用,其可能是通过抑制p38MAPK/NF-κB通路活化,抑制肾组织炎症反应而实现的。

Objective To explore the antagonistic effect of valsartan combined with amlodipine on mesangial hyperplasia in anti-Thy1 glomerulonephritis rats.Methods The anti-Thy 1 glomerulonephritis model was established by once injecting a rabbit anti-rat thymocyte immune serum via the tail vein.The successfully model rats were randomly divided into model,control,experimental and combined groups with 12 rats per group.Another 12 rats were injected with 0.9%NaCl as normal group.Control group was given 16 mg·kg^(-1)valsartan.Experimental group was given 10 mg·kg^(-1)amlodipine.Combined group was given 16 mg·kg^(-1)valsartan+10 mg·kg^(-1)amlodipine.Model and normal groups were given equal volume of 0.9%NaCl.Five groups were gavaged once daily for 14 days.The contents of 24 h urinary protein(24 h UP),blood urea nitrogen(BUN)and serum creatinine(SCr)in urine were detected by automatic biochemical analyzer.The levels of p38 mitogen activated protein kinase/nuclear transcription factorκB(p38 MAPK/NF-κB)in renal tissue were detected by Western blot.Results The 24 h UP of combined,experimental,control,model and normal groups were(2.03±0.31),(3.75±0.94),(3.68±0.92),(4.95±1.23)and(0.27±0.07)mg·d^(-1);the BUN were(13.16±3.29),(17.65±4.41),(17.94±4.49),(22.75±5.69)and(8.96±2.24)μmol·L^(-1);the SCr were(50.15±12.53),(62.05±15.51),(63.13±15.78),(83.27±20.82)and(40.15±10.03)μmol·L^(-1);p-p38MAPK/p38MAPK were0.51±0.13,0.70±0.17,0.72±0.18,0.99±0.25 and 0.21±0.05;the relative expression levels of NF-κB p65 protein were 0.55±0.14,0.79±0.20,0.81±0.21,1.12±0.28 and 0.18±0.05,respectively.The above indexes of experimental,control and combined groups were significantly lower than those in model group and the differences were statistically significant(all P<0.05).Also,comparing with combined group,the above indexes of experimental and control groups were significantly lower in the experimental and control groups(all P<0.05).Conclusion Valsartan combined with amlodipine has an antagonistic effect on mesangial hyperplasia in anti-Thy1 glomerulonephritis rats,which may be achieved through inhibition of p38MAPK/NF-κB pathway activation and subsequent inhibition of inflammatory response in renal tissue.