Study on mechanism of the regulation of mitochondrial autophagy by Hewei Liqi Decoction on gastrointestinal motility disorders in functional dyspepsia based on PINK1 / Parkin pathway
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 6
Abstract
Objective To observe the effects of Hewei Liqi Decoction on gastrointestinal motility and PINK1 / Parkin signaling pathway in functional dyspepsia ( FD ) rat model with liver-stomach disharmony, and to explore its regulatory mechanism on mitochondrial autophagy. Methods Forty healthy Wistar rats were randomly divided into blank control group, model control group, mosapride group, and Hewei Liqi Decoction group, with 10 rats in each group. Except for the blank control group, the other groups were made into FD rat model with liver-stomach disharmony by clipping tails. After the model was established, the Hewei Liqi Decoction group and the mosapride group were treated with medication. The general state, water intake, food intake and organic changes on the surface of gastric mucosa were observed. The gastric emptying rate and small intestinal propulsion rate were detected to evaluate the gastrointestinal motor function. HE staining was used to observe the pathological changes of gastric antrum such as erosion, ulceration, metaplasia, atrophy and atypical hyperplasia. Immunofluorescence staining was used to detect the changes of mitochondrial autophagy in gastric tissues, JC-1 flow cytometry technology to detect the changes of mitochondrial membrane potential, enzyme linked immunosorbent assay to analyze the content of mitochondrial adenine nucleoside triphosphate ( ATP) and the level of reactive oxygen species (ROS), and Western blotting to detect the expressions of mitochondrial autophagy protein PINK1, LC3, Parkin, and P62. Results Compared with the blank control group, the water intake and food intake of the model control group significantly decreased (all P < 0. 05), the gastric emptying rate and small intestinal propulsion rate slowed down (all P < 0. 05), CYT-C quickly expressed in gastric tissues, LC3B expression significantly accumulated, mitochondrial membrane potential downregulated (P < 0. 05), the proportion of mitochondrial membrane potential changes significantly up-regulated (P < 0. 05), the ability of mitochondria to generate ATP significantly down-regulated (P < 0. 05), mitochondrial ROS levels significantly increased (P < 0. 05), and the expression of mitochondrial autophagy protein PINK1, Parkin, P62 and LC3 significantly increased (all P < 0. 05). Compared with the model control group, the water intake and food intake of rats in the mosapide group and Hewei Liqi Decoction group increased significantly (all P < 0. 05), the gastric emptying rate and small intestinal propulsion rate increased significantly ( all P < 0. 05 ), the expression of CYT-C was inhibited, LC3B accumulation decreased significantly, mitochondrial membrane potential up-regulated significantly (P < 0. 05), the proportion of changes of mitochondrial membrane potential down-regulated significantly (P < 0. 05), the ability of mitochondria to generate ATP up-regulated significantly (P < 0. 05), mitochondrial ROS levels significantly down-regulated (P < 0. 05), the ROS level of Hewei Liqi Decoction group was down-regulated more significantly ( P < 0. 01 ), and the expression of mitochondrial autophagy protein PINK1, Parkin, P62 and LC3 significantly down-regulated ( all P < 0. 05). Conclusion There are gastrointestinal motility disorders in FD, and Hewei Liqi Decoction increases gastrointestinal motility and improves the symptoms of FD rats with liver-stomach disharmony by regulating mitochondrial autophagy mediated by PINK1/ Parkin signaling pathway.
Authors and Affiliations
BAI Lu
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