小檗碱对肾动脉粥样硬化发生、发展的干预作用

Effects of berberine on amelioration of renal artery damage caused by atherosclerosis

目的:探讨高胆固醇饮食对大鼠肾动脉的影响及小檗碱对肾动脉粥样硬化发生、发展的干预作用。方法:选用SPF级雄性Wistar大鼠30只,随机分为对照组、模型组和小檗碱组,每组10只,后两组给予高脂饲料喂养12周,小檗碱组给予小檗碱(100 mg/kg)灌胃,模型组按等比重的生理盐水灌胃,共6周,对照组常规饮食进水外不予以任何处理,实验结束后禁食24 h利多卡因麻醉,抽取静脉血,提取血清,测定空腹血甘油三酯、胆固醇、低密度脂蛋白胆固醇等生化指标,取左侧肾动脉,行HE染色观察肾动脉组织病理改变,免疫组化观察肾动脉α-平滑肌肌动蛋白(α-SMA)表达,行RT-PCR及Western blot测定肾动脉的白介素(IL)-18 mRNA及蛋白表达。结果:模型组血生化指标与对照组、小檗碱组比较明显增高,差异具有统计学意义(P<0.05),HE染色及α-SMA免疫组化示模型组大鼠肾动脉组织内膜增生及斑块形成,内膜下可见泡沫细胞及平滑肌细胞堆积;小檗碱组内膜组织轻度增厚剥脱,内膜下少量泡沫细胞,平滑肌细胞增多不明显。结论:小檗碱可能通过调节大鼠的血脂水平和抑制细胞因子IL-18的表达来改善肾动脉粥样硬化的发生发展。

Objective： To investigate the effect of high-cholesterol diet on renal artery atherosclerosis and the amelioration of berberine. Methods： Thirty SPF male Wistar rats were randomly divided into control group （n = 10）,experimental group （n = 10） and bcrberine group （n = 10）. Rats of control group were fed with normal diets while the other two groups were fed with high choles- terol diet starting from the second week for 3 months,after which the berberine group were administrated berberine （100 mg/kg） through intragastrie administration daily, and the rats from experimental group were given normal saline for totally 6 weeks. Lidoeaine was used for anesthesia and blood biochemical parameters such as cholesterol and creatinine were checked. Hematoxylin and Eosin （HE） staining and immunohistochemistry were used to investigate the effect of berberine on the AS lesion of renal artery. RT-PCR and Western blotting was used to study the expression of the IL-18 mRNA and protein. Results： Some of the blood biochemistry pa- rameters of experimental group were significantly different from the other two groups （P 〈 0.01）. The rats of experimental group have generated a significant accumulation of the foam cells and migration of the smooth muscle cells compared with that of the control group,while rats treated with the berberine showed less accumulation of the foam cells and no significant migration of the smooth muscle cells. The relative expression of the IL-18 mRNA increased significantly after induction of renal artery AS compared with that of the control group and the berberine group （both P 〈 0.01）. Conclusion： Berberine can suppress the expression of IL-18 and prevent the formation and development of the AS, consequently protect the renal artery,renal artery stenosis and the damage from renal artery stenosis.