栽培桑黄对FSGS肾病大鼠肾功能及肾纤维化机制研究

Interventional Effect and Mechanism of Phellinus Baumii on Renal Function and Renal Fibrosis in FSGS Rats

目的:研究栽培桑黄对局灶节段肾小球硬化(focal stage glomerulosclerosis, FSGS)肾病大鼠早期肾损伤的干预作用及其机制。方法:采用单侧肾切除合并尾静脉注射阿霉素构建FSGS大鼠模型,分别用人工桑黄水煎剂及水提物进行干预治疗。生化检测尿蛋白、血肌酐、尿素氮、血脂及其他指标,Masson染色观察肾组织病理损伤情况,RT-PCR检测肾皮质Col-Ⅳ、FN、MMP9、TIMP-1基因表达水平。结果:和模型组比较,桑黄水煎剂低剂量组可显著降低24 h尿蛋白、血肌酐、尿素氮、三酰甘油、胆固醇的水平(P<0.05)。桑黄水煎剂、水提物均可降低心肌酶或谷丙转氨酶水平,其中水煎剂低剂量组心肌酶显著低于模型组(P<0.05),水提物高剂量组显著降低心肌酶和谷丙转氨酶水平(P<0.05)。桑黄水煎剂低剂量可显著下调Col-Ⅳ、FN的mRNA水平(P<0.05),上调MMP9/TIMP-1水平(P<0.05)。结论:桑黄可显著降低尿蛋白,改善肾功能和肾组织病理损伤,降低细胞外基质沉积,且相同生药剂量的桑黄传统水煎剂好于水提物疗效,其机制可能与其调节金属蛋白酶及其抑制剂表达有关。

Objective:To investigate the effect of Phellinus baumii(Mesima) on renal function and mechanism of early renal injury in focal segmental glomerulosclerosis(FSGS) rats. Methods:Rat model with FSGS was established by unilateral nephrectomy combined with adriamycin injection into the tail vein, and intervention with Phellinus baumii decoction(PBD) and Phellinus baumii water extract(PBW). Biochemical detected the changes of urine protein、serum creatinine、urea nitrogen、blood lipids and other indicators, Masson staining observed the changes of renal tissue pathological damage. RT-PCR detected the expression of Col-Ⅳ、FN、MMP9、TIMP-1 in kidney cortex tissues. Results:Compared with the model group, the urine protein, serum creatinine, urea nitrogen, triglycerides and cholesterol levels decreased significantly in the low dose of Phellinus baumii decoction(PBD-LD)(P<0.05). Both the PBD and PBW could reduce the myocardial enzyme or ALT enzyme level. The myocardial enzymes in PBD-LD group were significantly lower than the model group(P<0.05). The high-dose group of water extract(PBW-HD) significantly reduced the level of myocardial enzymes and ALT enzymes(P<0.05). PBD-LD group can significantly reduce the mRNA levels of Col-Ⅳ and FN and up-regulated MMP9/TIMP-1 level(P<0.05). Conclusion:The same raw dose of PBD is better than the PBW;Phellinus baumii can significantly reduce urine protein, improve renal function and pathological damage of renal tissue, and reduce extracellular matrix deposition. The mechanism may be related to the regulation of metalloproteinase and its inhibitor expression.