肾复康Ⅱ号胶囊对IgA肾病大鼠血清醛固酮及肾内小动脉病变的影响

Effects of ShenfukangⅡcapsule on aldosterone and intrarenal arterioles in IgAN rats

目的:观察肾复康Ⅱ号胶囊对IgA肾病(IgAN)肾内小动脉病变大鼠醛固酮诱导的血管内皮细胞生长因子(VEGF)、增殖细胞核抗原(PCNA)、人基质金属蛋白酶-9(MMP-9)的表达,探讨肾复康Ⅱ号胶囊对IgAN小动脉病变的防治机制。方法:将70只健康雄性SD大鼠分为空白组、模型组、治疗组(肾复康组)、中药对照组(黄葵组)、西药对照组(螺内酯组),采用0.9%氯化钠水溶液灌胃+皮下注射CCl_(4)+静脉注射脂多糖建造IgAN大鼠模型。空白组、模型组给予0.9%氯化钠水溶液灌胃,余组给予相应药物灌胃,给药后4、8、12周时点检测大鼠24 h尿蛋白定量,12周时点检测大鼠肾脏指标、血清醛固酮、AngⅡ,免疫组织化学Envision System二步法检测大鼠小动脉区域VEGF、MMP-9、PCNA,检测IgAN造模大鼠肾组织内膜/血管外径值、中膜/血管外径值、管壁/血管外径值。结果:与同时点模型组相比,三组24 h U-TP均下降,血肌酐及尿素氮水平降低,血清醛固酮肾复康组与两对照组比较差异明显。内膜及管壁/血管外径值明显减小(P<0.05),管壁增厚与VEGF、PCNA、MMP-9的表达中度相关(0.5<r<0.8),血清醛固酮与VEGF、PCNA、MMP-9表达均呈中度正相关关系(0.5<r<0.8)。结论:肾复康Ⅱ号胶囊可通过抑制醛固酮,降低VEGF、MMP-9、PCNA表达,进一步抑制肾内小动脉血管内皮细胞增殖,减轻肾脏损伤。

Objective:To observe the expression of ShenfukangⅡcapsule on aldosterone-induced vascular endothelial cell growth factor(VEGF),proliferating cell nuclear antigen(PCNA)and human matrix metalloproteinase-9(MMP-9)in rats with IgA nephropathy(IgAN)intrarenal arteriopathy,and to explore the effect of ShenfukangⅡcapsule on IgAN arteriole disease prevention mechanism.Methods:70 healthy male SD rats were divided into blank group,model group,treatment group(Shenfukang group),traditional Chinese medicine control group(Huangkui group),western medicine control group(spironolactone group),and normal saline gavage+Subcutaneous injection of CCL_(4)+intravenous injection of lipopolysaccharide to build IgAN rat model.The blank group and the model group were given normal saline by gavage,and the remaining groups were given the corresponding drugs by gavage.The 24 h urine protein was measured at 4,8 and 12 weeks after the administration,and the rat’s kidney indexes were measured at 12 weeks.Serum aldosterone,AngⅡ,immunohistochemical Envision System two-step method to detect VEGF,MMP-9,PCNA in rat arterioles,and IgAN production model rat kidney tissue intima/vascular outer diameter value,media/vascular outer diameter value,tube wall/vascular outer diameter value.Results:Compared with the simultaneous point model group,the 24-hour U-TP of the three groups decreased,and the blood creatinine and urea nitrogen levels decreased.The serum aldosterone Shenfukang group was significantly different from the two control groups.Intima and vessel wall/vascular outer diameter values were significantly reduced(P<0.05),vessel wall thickening was moderately correlated with the expression of VEGF,PCNA,and MMP-9(0.5<r<0.8),serum aldosterone was correlated with VEGF,PCNA,The expressions of MMP-9 and showed a moderately positive correlation(0.5<r<0.8).Conclusion:ShenfukangⅡCapsule can inhibit the expression of VEGF,MMP-9 and PCNA by inhibiting aldosterone,further inhibiting the proliferation of intrarenal arteriole vascular endothelial cells and reducing kidney injury.