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蔡亚宏, 刘林券, 冯进, 蔡喆燚, 陈娟, 李莎, 熊丹.六味地黄汤调控TGF-β及Smad家族蛋白表达对肾间质纤维化的影响研究[J].湖南中医药大学学报英文版,2024,44(7):1145-1151.[Click to copy
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| 六味地黄汤调控TGF-β及Smad家族蛋白表达对肾间质纤维化的影响研究 |
| 蔡亚宏,刘林券,冯进,蔡喆燚,陈娟,李莎,熊丹 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探究六味地黄汤抑制肾间质纤维化（renal interstitial fibrosis, RIF）的干预作用及机制。方法 将30只SPF级SD大鼠随机均分为假手术组、模型组、阳性药物组、中药高剂量组和中药低剂量组，每组6只。除假手术组外，其余各组采用左侧输尿管结扎术制备RIF模型。造模结束后，假手术组和模型组予以蒸馏水灌胃，阳性药物组予以醋酸泼尼松片0.2 mg/kg灌胃，中药低、高剂量组分别予以六味地黄汤0.5、1 mg/kg灌胃，疗程为21 d。治疗结束后，采用HE染色法评估肾间质损伤，Masson染色法检测肾间质胶原蛋白沉积和纤维化，RT-PCR测定肾间质转化生长因子-β1（transforming growth factor-β1, TGF-β1）、针对半身不遂同源物2的重组母体（recombinant mothers against decapentaplegic homolog 2, Smad2）、Smad3、Smad7的mRNA表达，Western blot测定肾间质TGF-β1、Smad2、Smad3、Smad7的蛋白表达。结果 与假手术组相比，模型组的病理呈现系膜增生、间质增宽、胶原蛋白大面积沉积和明显纤维化，且TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均增加（P<0.05）。与模型组相比，阳性药物组和中药低、高剂量组的病理表现均减轻，且TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均降低（P<0.05）。与中药低剂量组相比，阳性药物组和中药高剂量组的TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均降低（P<0.05）。结论 六味地黄汤能够减轻RIF大鼠的肾间质纤维化程度，且高剂量效果更佳，其机制可能与调控TGF-β及Smad家族蛋白表达有关。 |
| 关键词: 六味地黄汤 肾间质纤维化 终末期肾病 肾间质损伤 TGF-β Smad家族蛋白 |
| DOI：10.3969/j.issn.1674-070X.2024.07.001 |
| Received:January 09, 2024 |
| 基金项目:湖南省自然科学基金项目（2020JJ4474）；湖南省卫生健康委员会科研计划项目（D202314018599，W20243021）；湖南中医药大学校院联合基金项目（2023XYLH044）。 |
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| Effects of Liuwei Dihuang Decoction on renal interstitial fibrosis by regulating the expressions of TGF-β and Smad family proteins |
| CAI Yahong, LIU Linquan, FENG Jin, CAI Zheyi, CHEN Juan, LI Sha, XIONG Dan |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the intervention effects and mechanism of Liuwei Dihuang Decoction (LWDHD) on inhibiting renal interstitial fibrosis (RIF). Methods A total of 30 SPF SD rats were randomly divided into sham-operated group, model group, positive drug group, high- and low-dose Chinese medicines groups, with six rats in each group. Except for the sham-operated group, all other groups were prepared with left ureteral ligation to establish RIF models. After modeling, the sham-operated group and model group were given distilled water by gavage, the positive drug group was given acetic acid prednisone tablets 0.2 mg/kg by gavage, and the high- and low-dose Chinese medicines groups were given LWDHD 1 mg/kg and 0.5 mg/kg by gavage, respectively, for a treatment course of 21 d. After treatment, renal interstitial injury was evaluated by HE staining, and renal interstitial collagen deposition and fibrosis were measured by Masson staining. The mRNA expressions of transforming growth factor-β1 (TGF-β1), recombinant mothers against decapentaplegic homolog 2 (Smad2), Smad3, and Smad7 were determined by RT-PCR. The protein expressions of TGF-β1, Smad2, Smad3, and Smad7 in the renal interstitium were determined by Western blot. Results Compared with the sham-operated group, the model group exhibited pathological features of mesangial proliferation, interstitial widening, and extensive collagen deposition and obvious fibrosis, as well as elevated mRNA and protein expressions of TGF-β1, Smad2, Smad3, and Smad7 (P<0.05). Compared with the model group, the positive drug group, low- and high-dose Chinese medicines groups showed alleviated pathological changes, as well as a decrease in the mRNA and protein expressions of TGF-β1, Smad2, Smad3, and Smad7 (P<0.05). Compared with the low-dose Chinese medicines group, the mRNA and protein expressions of TGF-β1, Smad2, Smad3, and Smad7 in the positive drug group and the high-dose Chinese medicines group decreased (P<0.05). Conclusion LWDHD can reduce renal interstitial fibrosis in RIF rats, with higher doses exhibiting more pronounced effects. The mechanism may be related to the regulation of TGF-β1 and Smad family protein expression. |
| Key words: Liuwei Dihuang Decoction renal interstitial fibrosis end-stage renal disease renal interstitial injury TGF-β Smad family protein |
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