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目的探讨大黄素对IgG型抗双链DNA(dsDNA)抗体诱导的大鼠系膜细胞(MCs)表型转化的抑制作用。方法利用马疫锥虫动基体DNA诱导大鼠产生IgG型抗dsDNA抗体,小牛胸腺DNA纤维素层析法提纯抗体。体外培养正常MCs(空白组),或在培养上清中分别加入IgG型抗dsDNA抗体、25 mg/L大黄素(对照组),或同时加IgG型抗dsDNA抗体与大黄素(实验组),检测MCs合成转化生长因子-β_1(TGF-β_1)、α-平滑肌肌动蛋白(α-SMA)等水平,并在透视电镜下观察细胞显微结构的变化。结果与空白组比较,抗体对照组合成TGF-β_1等水平明显升高(P<0.05),并出现肌成纤维细胞样结构变化;而大黄素对照组的上述指标下降(P<0.05),且细胞显微结构基本正常。与抗体对照组比较,实验组合成TGF-β_1等水平降低,细胞显微结构大致正常。结论抑制IgG型抗dsDNA抗体诱导的系膜细胞表型转化可能是大黄素治疗狼疮肾炎的药理机制之一。
Objective To investigate the inhibitory effect of emodin on phenotypic transformation of rat mesangial cells (MCs) induced by IgG anti-double stranded DNA (dsDNA) antibody. Methods The IgG-type anti-dsDNA antibody was induced in E. mobilis using matrix DNA from the horse worm, and the antibody was purified by calf thymus DNA cellulose chromatography. Culture normal MCs in vitro (blank group), or add IgG anti-dsDNA antibody, 25 mg/L emodin (control), or IgG anti-dsDNA antibody and emodin (experimental group) to the culture supernatant. The levels of TGF-β_1 and α-SMA in MCs were detected, and the changes of cell microstructure were observed under transmission electron microscope. Results Compared with the blank group, the antibody control combined TGF-β 1 level was significantly increased (P<0.05), and the myofibroblast-like structure was observed; however, the above indicators of the emodin control group decreased (P<0.05). The cell microstructure is almost normal. Compared with the antibody control group, the experimental combination of TGF-β_1 and other levels decreased, and the cell microstructure was approximately normal. Conclusion The inhibition of phenotypic cell transformation induced by IgG anti-dsDNA antibody may be one of the pharmacological mechanisms of emodin in the treatment of lupus nephritis.