甘西鼠尾草总酚酸提取物对嘌呤霉素氨基核苷大鼠足细胞损伤的保护作用

Protective effect of salvia przewalskii extract of total phenolic acids on puromycin aminonucleoside-induced rat podocyte injury

目的:研究甘西鼠尾草总酚酸提取物(SPE)对嘌呤霉素氨基核苷(PAN)大鼠足细胞损伤的保护作用。方法:建立PAN肾病大鼠动物模型,给予他克莫司和SPE干预治疗,分别在第5、10、15、21天留取血尿标本,同时采用肾组织病理观察大鼠肾小球组织形态学改变,透射电镜观察肾小球足细胞超微结构改变,并分别从mRNA和蛋白水平分析足细胞裂孔膜蛋白的表达水平。结果:(1)除正常组外,各组大鼠尿蛋白定量第5天时已明显升高,第10天上升至高峰,而后开始下降,第15天时仍明显高于正常。给予药物干预后,可降低大鼠的尿蛋白排泄量,且阳性对照组与SPE高剂量组降低尿蛋白的程度较为接近。(2)光镜下未见肾小球形态异常。电镜结果显示第5天时已出现肾小球足细胞足突融合,第10天时足突融合最明显,随后开始恢复,第21天基本恢复正常;SPE高剂量组和阳性对照组的足突融合程度较轻。(3)阳性对照组和SPE组大鼠的nephrin、podocin蛋白表达水平高于模型对照组。第5天时各组大鼠蛋白表达低于正常,第10天时下降更为明显,第15天蛋白表达已开始回升,至第21天时恢复至正常水平。阳性对照组和SPE高剂量组大鼠蛋白表达均明显高于其余三组。(4)大鼠nephrin、podocin的mRNA表达量在第5天时已下降,至第10天明显下降至最低水平,而后开始上升,直至第21天恢复至正常水平。阳性对照组和SPE高剂量组的表达水平明显高于其他各组(P<0.05)。结论:SPE对PAN大鼠肾小球足细胞损伤有一定的保护作用,可降低PAN大鼠蛋白尿。

Objective：To determine the effect of Salvia Przewalskii extract （ SPE） on Puromycin Aminonucleoside （ PAN）-induced rat podocytes injury. Methodology：The rats were divided into six groups, and each group was 12 rats. They were treated with either PAN only or PAN followed by tacrolimus or low-, medium-, high-dose SPE and normal control. The effects of SPE on podocyte injury 5, 10, 15 and 21 days following treatment were evaluated. Results：1） Proteinuria was observed starting on day 5 except in normal control group. The peak levels of proteinuria were different among the groups with tacrolimus, and high-dose SPE significantly decreased proteinuria relative to the PAN and low-and medium-dose SPE groups. The proteinuria in each group was decreased after 15 days and returned to a normal level after 21 days. 2） With electron microscopy, the foot process effacement was observed starting on day 5, but that was lighter in the tacrolimus and high-dose SPE groups. 3） In IHC staining, the increasing expressions and better linear distributions of nephrin and podocin were revealed in the high-dose SPE and tacrolimus groups. Those results were also confirmed by Western blot analysis. 4） The mRNA levels of nephrin and podocin in the tacrolimus and high-dose SPE groups were significantly higher than that of the other groups on day 5, 10, and 15. Conclusion：SPE can protect podocytes from PAN-induced injury.