不同调脂方案对大鼠动脉硬化模型肝肾功能及免疫反应相关因子的影响

Influence of different lipid regulation schemes on hepatic and renal functions and immunoreaction related factors in rat model of arteriosclerosis

目的探讨不同调脂方案对大鼠动脉硬化模型肝肾功能及免疫反应相关因子的影响。方法选取42只6周龄健康雄性大鼠Wistar(210±10)g,将其随机分为5组:正常对照组(N组)、高脂模型组(C组)、低剂量辛伐他汀(10 mg/kg·d)组(S组)、较高剂量辛伐他汀(20 mg/kg·d)组(SH组)和低剂量辛伐他汀(10 mg/kg·d)联合依折麦布(5 mg/kg·d)组(SE组)。给药组分别给予相应剂量的降脂药物灌胃4周。于给药前后分别测定血脂,肝肾功能指标以及干扰素-r(IFN-r)、白细胞介素-4(IL-4)水平。结果药物处理组(S组、SH组、SE组)血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平较高脂模型组差异均明显降低(P<0.05),其中以SE组减低最为明显。药物处理组(S组、SH组、SE组)尿素氮(BUN)、尿酸(UA)、尿蛋白浓度(U-pro)水平明显降低,血清激酶清除率(Ccr)水平较高脂模型组差异均升高(P<0.05),其中以SH组最显著。高脂组大鼠血清IFN-r水平升高,SH组较S组及SE组更有效减低IFN-r水平,与高脂组比较差异显著(P<0.01)。IFN-r水平与三酰甘油、总胆固醇、低密度脂蛋白胆固醇呈正相关(P<0.05),与高密度脂蛋白胆固醇呈负相关(P<0.05)。结论小剂量辛伐他汀联合依折麦布治疗降低血脂作用显著,能有效改善高脂血症所诱发的肝功能异常;单用较大剂量辛伐他汀治疗更能有效保护肾脏功能;血清IFN-r水平同血脂水平有明确相关性;高剂量辛伐他汀治疗能明显降低大鼠血清IFN-r水平。

Objective To discuss the influence of different lipid regulation schemes on hepatic and renal functions and immunoreactions related factors in rat model of arteriosclerosis. Methods Health male Wistar rats (n=42, aged 6 w and weighed 210 g±10 g) were chosen, and divided into 5 groups: normal control group (N group),high-lipid model group (C group), low-dose simvatatin group (10 mg/kg·d, S group), high-dose simvatatin group (20 mg/kg·d, SH group), and low-dose simvatatin+ezetimibe group (10 mg/kg·d+5 mg/kg·d, SE group). All medication groups were orally given corresponding drugs for 4 w. The indexes of blood fat and hepatic and renal functions, and levels of interferon-r (IFN-r) and interleukin-4 (IL-4) were detected before and after medication.Results The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C),alanine aminotransferase (ALT) and aspertate aminotransferase (AST) decreased significantly in S group, SH group and SE group compared with C group, which was more significant in SE group. The levels of blood urea nitrogen (BUN), uric acid (UA) and urine protein (U-pro) decreased significantly in S group, SH group and SE group, and creatinine clearance rate (CCr) increased compared with C group, which was more significant in SH group. The level of serum IFN-r increased in C group, and decreased in SH group compared with S group and SE group (P<0.01).The level of serum IFN-r was positively correlated to levels of TG, TC and LDL-C (P<0.05), and was negatively correlated to high-density lipoprotein-cholesterol (HDL-C, P<0.05). Conclusion The lipid-lowering effect of low-dose simvatatin combining ezetimibe is significant, which can ameliorate abnormal hepatic function induced by hyperlipidemia, and high-dose simvatatin can effectively protect renal function. The level of serum IFN-r is definitely correlated to level of blood fat, and high-dose simvatatin can significantly decrease the level of serum IFN-r in rats.