Wu Liyan, Lu Zengsheng, He Beihui, Yu Jianshun, Yan Maoxiang, Jiang Jianping, Chen Zhiyun
Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
The Second Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
Anat Rec (Hoboken). 2023 Dec;306(12):3169-3177. doi: 10.1002/ar.25117. Epub 2022 Dec 9.
Nonalcoholic steatohepatitis (NASH) is a critical stage in the prognosis of nonalcoholic fatty liver disease (NAFLD). Pure total flavonoids from circus (PTFC) play essential roles in the improvement of NASH symptoms, but the underlying regulatory mechanism remains elusive. Our previous high-throughput omics screening results indicate that the CCL2/CCR2-PI3K-Akt signaling pathway is a key pathway that regulates the liver inflammatory response. PTFC may regulate the CCL2/CCR2-PI3K-Akt signaling pathway to improve the liver inflammatory response.
A mice model of NASH was established by a high-fat diet, and PTFC was used as treatment. Hematoxylin-eosin and oil red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real-time PCR were used to measure the mRNA and protein levels in the liver. The expression of proinflammatory cytokines in the peripheral blood and liver tissues was measured by liquid suspension array. An automatic biochemical method was used to examine serum transaminases and lipids levels, as well as liver lipids.
Compared with the mice in the high-fat diet group, mice in the HFD + PTFC group showed significantly improved liver histopathology, and levels of serum transaminase and lipids, liver lipids and serum proinflammatory cytokines. Moreover, the mRNA and protein expression and phosphorylation levels of key signaling molecules in the CCL2/CCR2-PI3K-Akt signal transduction pathway were obviously reduced by PTFC treatment.
PTFC can ameliorate NASH symptoms, and the mechanism may be related to regulating the CCL2/CCR2-PI3K-Akt signal transduction pathway to reduce the liver inflammatory response.
非酒精性脂肪性肝炎（NASH）是非酒精性脂肪肝病（NAFLD）预后的关键阶段。刺儿菜总黄酮（PTFC）在改善NASH症状方面发挥着重要作用，但其潜在的调控机制仍不清楚。我们之前的高通量组学筛选结果表明，CCL2/CCR2-PI3K-Akt信号通路是调节肝脏炎症反应的关键通路。PTFC可能通过调节CCL2/CCR2-PI3K-Akt信号通路来改善肝脏炎症反应。
通过高脂饮食建立NASH小鼠模型，并使用PTFC进行治疗。采用苏木精-伊红染色和油红O染色观察肝组织的病理变化。采用蛋白质免疫印迹法和实时荧光定量PCR检测肝脏中的mRNA和蛋白质水平。采用液相悬浮芯片检测外周血和肝组织中促炎细胞因子的表达。采用自动生化方法检测血清转氨酶、血脂水平以及肝脏脂质。
与高脂饮食组小鼠相比，高脂饮食+PTFC组小鼠的肝脏组织病理学、血清转氨酶和血脂水平、肝脏脂质以及血清促炎细胞因子水平均有显著改善。此外，PTFC处理明显降低了CCL2/CCR2-PI3K-Akt信号转导通路中关键信号分子的mRNA和蛋白质表达及磷酸化水平。
PTFC可改善NASH症状，其机制可能与调节CCL2/CCR2-PI3K-Akt信号转导通路以减轻肝脏炎症反应有关。
