Role of pinkl/parkin-mediated mitochondrial autophagy in a rat model of brain injury / 中国组织工程研究

ABSTRACT

BACKGROUND: In addition to FUNDC1, Bnip3 and Nix mitochondrial autophagy pathways in mammals that are closely related to the hypoxic environment, Pinkl/Parkin is the main mitochondrial autophagy pathway after brain injury. PINK1 acts upstream of Parkin, and the Pinkl/Parkin pathway is used to mediate loss of mitochondrial surface functional proteins or structural polyubiquitination, and considered as a marker for autophagosome selection, which has an important influence on autophagy-dependent degradation of depolarized mitochondria. OBJECTIVE: To analyze the role of Pinkl/Parkin-mediated mitochondrial autophagy in rats with brain injury after hypertensive intracerebral hemorrhage. METHODS: The study was approved by the Laboratory Animal Ethical Committee of North Sichuan Medical College. Forty-five male Wistar rats of SPF grade were randomly divided into normal, model and autophagy inhibitor groups. The rats in the model and autophagy inhibitor groups were used to prepare hypertensive cerebral hemorrhage model. Before modeling 2 µL of PBS solution containing trimethyl adenine (100 nmol/L) was intraperitoneally injected in the inhibitor group, and the model and the normal groups were intraperitoneally injected with 2 µL of PBS. The water content, mitochondrial autophagy, mitochondrial membrane potential, cerebral infarction, mitochondrial LC3, Parkin protein and PINK1 protein expression in brain tissue were detected. RESULTS AND CONCLUSION: (1) Compared with the normal group, the autophagy staining and mitochondrial staining expression in the model group was increased, and the number of co-localized positive cells was increased (both P < 0.05). Compared with the model group, the autophagy staining and mitochondrial staining expression in the autophagy inhibitor group was decreased, and the number of co-localized positive cells was decreased (both P < 0.05). (2) Compared with the normal group, the infarction proportion of the brain in the model group was increased (P < 0.05). Compared with the model group, the infarction proportion of the brain in the autophagy inhibitor group was increased (P < 0.05). (3) Compared with the normal group, the mitochondrial staining intensity in the model group was decreased, and the autophagy staining intensity was increased (both P < 0.05). Compared with the model group, the mitochondrial staining intensity in the autophagy inhibitor group was decreased, and the autophagy staining intensity was increased (both P < 0.05). (4) Compared with the normal group, the expression levels of PINK1, LC3 and Parkin in the model group were increased (P < 0.05). Compared with the model group, the expression levels of PINK1, LC3 and Parkin in the autophagy inhibitor group were decreased (P < 0.05). In summary, mitochondrial autophagy can alleviate the degree of brain injury after hypertensive intracerebral hemorrhage. The Pinkl/Parkin pathway plays an important role in the mitochondrial autophagy.