Xu Lianjie, Zhang Yurong, Ji Nengbo, Du Yan, Jia Tao, Wei Shanshan, Wang Wei, Zhang Shan, Chen Wenhui
Faculty of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650500, P.R. China.
Department of Orthopedics, First Clinical Medical College of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650021, P.R. China.
Exp Ther Med. 2022 Jun 1;24(1):486. doi: 10.3892/etm.2022.11413. eCollection 2022 Jul.
Tanshinone IIA (TIIA) is a major component extracted from the traditional herbal medicine and has been indicated to play a role in the treatment of organ fibrosis. However, the evidence supporting its antifibrotic effect is insufficient and the underlying mechanism is unclear. To investigate the therapeutic effect of TIIA on non-alcoholic steatohepatitis-related fibrosis (NASH-F), the present study used a methionine choline deficiency diet to induce NASH-F in rats, and explored the effect of TIIA on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. Wistar rats were randomly divided into control, NASH-F and TIIA groups. After 8 weeks of treatment, the levels of serum markers associated with liver function and fibrosis were measured, liver fat vacuoles and inflammation were assessed by haematoxylin and eosin staining, and liver fibrosis was assessed by Masson's trichrome staining. TGF-β1, Smad2, Smad3, Smad7 and α-smooth muscle actin (α-SMA) mRNA expression, and TGF-β1, Smad2/3, phosphorylated (p)-Smad2/3, Smad7 and α-SMA protein levels were determined. The results revealed that TIIA could remarkably ameliorate liver fat vacuoles and inflammation in NASH-F rats, and could decrease the levels of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, total bile acid, hyaluronic acid, type Ⅳ collagen, laminin and type III collagen, while increasing the levels of total cholesterol and triglycerides; however, this was not statistically significance. TIIA markedly suppressed the increased TGF-β1, Smad2, Smad3 and α-SMA mRNA expression levels observed in the liver of NASH-F rats, while it increased the mRNA expression level of Smad7. Similarly, TIIA suppressed the increased TGF-β1, p-Smad2/3 and α-SMA protein levels observed in the liver of NASH-F rats, while it increased the protein expression level of Smad7 and . TIIA had no significant cytotoxic effect at 10, 20, 40 and 80 µmol/l on human LX-2 cell. In conclusion, the findings of the present study indicated that TIIA alleviated NASH-F by regulating the TGF-β1/Smad signaling pathway. TIIA may be a useful tool in the prevention and treatment of NASH-F.
丹参酮IIA（TIIA）是从传统草药中提取的主要成分，已被证明在器官纤维化治疗中发挥作用。然而，支持其抗纤维化作用的证据不足，其潜在机制尚不清楚。为了研究TIIA对非酒精性脂肪性肝炎相关纤维化（NASH-F）的治疗效果，本研究采用蛋氨酸胆碱缺乏饮食诱导大鼠发生NASH-F，并探讨TIIA对转化生长因子-β1（TGF-β1）/Smad信号通路的影响。将Wistar大鼠随机分为对照组、NASH-F组和TIIA组。治疗8周后，检测与肝功能和纤维化相关的血清标志物水平，通过苏木精和伊红染色评估肝脏脂肪空泡和炎症情况，通过Masson三色染色评估肝纤维化情况。测定TGF-β1、Smad2、Smad3、Smad7和α-平滑肌肌动蛋白（α-SMA）的mRNA表达水平，以及TGF-β1、Smad2/3、磷酸化（p）-Smad2/3、Smad7和α-SMA的蛋白水平。结果显示，TIIA可显著改善NASH-F大鼠的肝脏脂肪空泡和炎症，降低血清天冬氨酸转氨酶、丙氨酸转氨酶、总胆红素、总胆汁酸、透明质酸、Ⅳ型胶原、层粘连蛋白和III型胶原水平，同时升高总胆固醇和甘油三酯水平；然而，这一差异无统计学意义。TIIA显著抑制NASH-F大鼠肝脏中TGF-β1、Smad2、Smad3和α-SMA mRNA表达水平的升高，同时提高Smad7的mRNA表达水平。同样，TIIA抑制NASH-F大鼠肝脏中TGF-β1、p-Smad2/3和α-SMA蛋白水平的升高，同时提高Smad7的蛋白表达水平。TIIA在10、20、40和80 µmol/l浓度下对人LX-2细胞无明显细胞毒性作用。总之，本研究结果表明，TIIA通过调节TGF-β1/Smad信号通路减轻NASH-F。TIIA可能是预防和治疗NASH-F的有效药物。
