从抑制肾纤维化角度研究健脾清化方对阿霉素肾病大鼠肾功能的作用与机制

Effect and Mechanism of Jianpi Qinghua Recipe on Renal Functions of Adriamycin-induced Nephropathic Rats from the Angle of Inhibiting Renal Fibrosis

目的从成纤维细胞被激活向肌成纤维细胞(myofibroblast,MyoF)转化角度,探讨健脾清化方对阿霉素致局灶节段硬化(focal segmental glomurular sclerosis,FSGS)模型大鼠肾纤维化的影响。方法 56只SD大鼠,随机分为正常组(8只),假手术组(8只)和模型组(40只)。采用左侧肾切除加尾静脉注射阿霉素制备大鼠肾脏局灶节段性硬化模型,将造模成功后的大鼠分为模型组、健脾清化方组、健脾方组、清化方组和尿毒清组,每组8只,共5组,每组给予相对应的药物,每次2 mL,共56天。观察健脾清化方对模型大鼠血清肌酐、尿素氮、24 h尿蛋白定量、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)mRNA、Ⅲ型胶原(collagen typeⅢ,ColⅢ)mRNA、纤维连接蛋白(fibronectin,FN)mRNA、Ⅳ型胶原(collagen typeⅣ,ColⅣ)mRNA的影响。结果健脾清化方能显著降低血清肌酐、尿素氮及24 h尿蛋白定量(P<0.01);亦可明显降低α-SMA、ColⅢ、FN、ColⅣmRNA水平(P<0.01),且优于尿毒清组。与健脾方组比较,健脾清化方组和清化方组ColⅢ、FN mRNA表达水平明显降低(P<0.01)。结论健脾清化方对阿霉素肾病模型大鼠的肾功能和肾脏纤维化有改善作用,且疗效优于尿毒清和健脾方,该机制可能与健脾清化方抑制成纤维细胞的激活有关。

Objective To explore the effect of Jianpi Qinghua Recipe （JQR） on renal functions of adriamycin-induced focal segmental glomerular sclerosis （FSGS） rats from the angle of activating fibro- blasts to myofibroblast （MyoF）. Methods Totally 56 rats were randomly divided into the normal control group （n =8）, the sham-operation group （n =8）, and the model group （n =40）. The FSGS rat model was induced by nephrectomy of left kidney plus intravenous injection of adriamycin. Successfully modeled rats were further divided into 5 groups, i.e., the model group, the JQR group, the JPR （Jianpi Recipe） group, the QHR （Qinghua Recipe） group, and the NDQ （Niaoduqing） group, 8 in each group. Corresponding drugs were administered to rats in all groups, 2 mL each time, for 56 days. The effect of JQR on serum creatinine （SCr）, urea nitrogen, 24-h urinary protein excretion, α-smooth muscle actin （α-SMA） mRNA, collagen type Ⅲ （Col Ⅲ） mRNA, fibronectin （FN） mRNA, and collagen type Ⅳ （Col Ⅳ） mRNA were observed. Results JQR could significantly lower SCr, urea nitrogen, and 24-h urinary protein excretion levels （P 〈0.01 ）, and significantly decrease mRNA levels of α-SMA, Col Ⅲ, FN, and Col Ⅳ （P 〈0. 01 ）. It was advantageous over the NDQ group. Compared with JPR, the relative expression levels of Col Ⅲ mRNA and FN mRNA of JQR and QHR were significantly lower （P 〈 0.01 ）. Conclusions JQR could improve the renal function and renal fibrosis in the adriamycin-induced nephropathic model rats. Its efficacy was superior to that of NDQ. Its mechanisms might be linked with inhibiting activation of fibroblasts.