Effect of Rapamycin on rats with non-alcoholic fatty liver disease
TAN Liping1 CHEN Wenhui2 SHI Anhua3 WU Junzi1 ZHU Xiaosong1 ZHANG Shan1
1.Basic Medical College, Yunnan University of Chinese Medicine, Yunnan Province, Kunming 650500, China;
2.Yunnan Provincial Academician Expert Workstation 2019IC020, Yunnan University of Chinese Medicine, Yunnan Province, Kunming 650500, China;
3.Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan 20190720, Yunnan University of Chinese Medicine, Yunnan Province, Kunming 650500, China
Abstract：Objective To investigate the effect of Rapamycin on rats with non-alcoholic fatty liver disease (NAFLD) and its mechanism. Methods Twenty-four clean grade male SD rats, weighing 180-220 g, were selected, and eight of them were randomly selected as normal group and fed ordinary diet. The remaining 16 animals were fed high-sugar and high-fat diet to construct NAFLD model. Six weeks later, the model was successfully built, and after this, they were divided into model group and Rapamycin group according to random number table method, with eight animals in each group. Rapamycin group was given 2.8 mg/(kg·d) of Rapamycin intragastric administration, normal group and model group were given the same amount of normal saline intragastric administration for four weeks. After the experiment, hematoxylin-eosin staining and oil red O staining were used to observe the pathological changes of liver tissues in each group. Serum total cholesterol (TC), triglyceride (TG), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) levels, and liver tissue TC and TG levels were detected and compared among all groups. The expression levels of autophagy associated protein (Beclin1, ATG5), microtubule associated protein 1 light chain 3B (LC3B)-Ⅱ / LC3B-Ⅰ, and ubiquitin binding protein p62 in liver tissues of all groups were detected and compared. Results No obvious abnormality was observed in the morphology of liver cells in the normal group. In the model group, hematoxylin-eosin staining showed that there were fat vacuoles of different sizes in most liver cells, and oil red O staining showed that lipids in most liver cells were dyed orange. In Rapamycin group, there were less fat vacuoles and orange-red in liver tissue by hematoxylin-eosin staining and oil red O staining. Serum TC, TG, LDL-C, GOT, GPT, and liver tissue TC and TG levels in model group were higher than that in normal group, while serum HDL-C level was lower than that in normal group (P ＜ 0.05 or P ＜ 0.01). Serum TC, TG, LDL-C, and HDL-C levels in Rapamycin group were higher than those in model group, while serum GOT, GPT, and liver TC and TG levels were lower than those in model group (P ＜ 0.05 or P ＜ 0.01). The expression levels of Beclin1, LC3B-Ⅱ/ LC3B-Ⅰ, and ATG5 in the model group were lower than those in the normal group, while ubiquitin binding protein p62 was higher than that in the normal group (P ＜ 0.05). The expression levels of Beclin1, LC3B-Ⅱ/ LC3B-Ⅰ, and ATG5 in Rapamycin group were higher than those in model group, while ubiquitin binding protein p62 was lower than that in model group (P ＜ 0.05 or P ＜ 0.01). Conclusion Rapamycin has protective effect on NAFLD rats, and its mechanism may be related to enhance the level of autophagy in liver tissue.
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