Yang Peng-Chun, Bai Wei-Zhe, Wang Jing, Yan Cai-Hua, Huang Wei-Feng, Jiang Shi-Zhu
Department of Digestive Medicine, Affiliated Renhe Hospital of Three Gorges University, Yichang 443001, China.
The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai 519000, China.
Evid Based Complement Alternat Med. 2020 Nov 26;2020:2083697. doi: 10.1155/2020/2083697. eCollection 2020.
Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism.
Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry.
Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis ( < 0.05). Each dose of SSTF also significantly reduced TGF-1 protein expression and mRNA levels in the liver tissues ( < 0.05). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels ( < 0.05). Immunohistochemistry showed that each dose of SSTF reduced TGF-1 protein expression ( < 0.05).
Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-1/Smad7 pathway.
血吸虫病是一种影响全球超过1.42亿人的寄生虫病。血吸虫病的主要死亡原因包括肝肉芽肿和严重纤维化导致的继发性肝硬化。尽管进行了深入研究，但控制与血吸虫病相关的肝纤维化仍然具有挑战性。总黄酮（SSTF）是一种有望减轻肝纤维化的药物，但其作用机制尚不清楚。因此，本研究的目的是验证其对血吸虫病所致肝纤维化的影响，并探索其潜在的分子机制。
将60只雄性Sprague-Dawley大鼠随机分为六组：一组为正常对照组，五组为日本血吸虫诱导的肝纤维化组，分别给予或不给予SSTF或秋水仙碱治疗，后者作为阳性对照。采集每只动物的肝脏组织，观察肝纤维化的程度和分级。我们还使用RT-qPCR、蛋白质免疫印迹和免疫组织化学方法检测转化生长因子-β1（TGF-1）和Smad7的表达。
与未治疗的模型组相比，所有三个测试剂量的SSTF治疗组的肝纤维化均显著减轻（<0.05）。各剂量的SSTF还显著降低了肝组织中TGF-1蛋白表达和mRNA水平（<0.05）。相反，中、高剂量的SSTF显著增加了Smad7蛋白表达和mRNA水平（<0.05）。免疫组织化学显示，各剂量的SSTF均降低了TGF-1蛋白表达（<0.05）。
我们的结果表明，SSTF通过抑制TGF-1/Smad7通路减轻了日本血吸虫诱导的肝纤维化。
