熊果酸对阿霉素肾病小鼠肾脏病变的影响

Intervention effect of ursolic acid on adriamycin-induced nephropathy in mice

目的研究熊果酸(ursolic acid,UA)对小鼠阿霉素肾病(adriamycin-induced nephropathy,ADN)的影响,探讨其可能的机制。方法 40只Balb/c小鼠,随机分为正常对照组(Normal组),阿霉素肾病组(ADN组),低剂量熊果酸组(LU+ADN组),高剂量熊果酸组(HU+ADN组)。单次注射阿霉素创建阿霉素肾病模型,以熊果酸为干预因素,测定尿蛋白总量,苏木素-伊红(HE)染色观察肾脏病变情况,免疫组织化学法检测TGF-β1在肾小管间质中的表达。结果 1)小鼠24h尿蛋白总量:ADN组小鼠较Normal组显著升高(P<0.05),HU+ADN组较ADN组显著下降(P<0.05)。2)HE染色:ADN组出现显著的肾小管上皮细胞肿胀,管腔扩张等病变。与ADN组相比,HU+ADN组肾小管间质病变较轻。3)免疫组化染色半定量分析:(1)与Normal组比,ADN组肾间质表达TGF-β1显著增加,差异有统计学意义(P<0.05)。(2)与ADN组比,LU+ADN组TGF-β1表达差异无统计学意义(P>0.05);HU+ADN组小鼠TGF-β1表达显著下降,两组差异具有统计学意义(P<0.05)。结论高剂量熊果酸(50mg/kg)可以减少阿霉素肾病小鼠的尿蛋白,抑制阿霉素肾病小鼠肾小管间质TGF-β1蛋白的表达,发挥肾脏保护作用。

Objective To investigate the effect and mechanism of ursolic acid on adriamycin-induced nephropathy in mice.Methods Forty Balb/c mice were randomly divided into control group(Normal group),ADN group,low dose of UA group(LU+ADN group),high dose of UA group(HU+ADN group).The ADN model was established by treating with a single tail vein injection of ADR,UA was regarded as the interference factor.The Normal group received a single tail vein injection of saline only.Twenty four-hour urine was collected by urine protein tests.HE staining was used to obverse the tubulointerstitial lesions,and immunohistochemical staining detected the expression of TGF-β1 in tubulointerstitium.Results 1)24-hour urinary protein excretion:At day 7 after ADR injection,albuminuria was most evident in ADN group as compared with Normal group(P<0.05),and was attenuated in HU+ADN group as compared with ADN group(P<0.05).2)HE staining:The renal tubulointerstitial lesions of ADN group mice were obvious,with swelling of tubular epithelial cells,tubular dilation obviously.The tubulointerstitial lesions of HU+ADN group mice were relatively relieved.3)The semi-quantitative analysis of immunohistochemical staining:Compared with Normal group,the expression level of TGF-β1 in renal tissue of ADN group was significantly increased(P<0.05).Compared with ADN group,difference of the expression level of TGF-β1 in renal tissue of LU+ADN group had no statistics significance(P>0.05).Compared with ADN group,the expression level of TGF-β1 in renal tissue of HU+ADN group was significantly reduced(P <0.05).Conclusion The high concentration of UA(50 mg/kg)has a protection effect on mice with adriamycin-induced nephropathy by reducing urinary protein excretion and inhibiting the TGF-β1 protein expression in tubulointerstitial.