动物造模 z-bio 2022-04-24 591

　　Objective To investigate the neuroprotective effect of Tongxinluo capsule on cognitive impairment in rats exposed to acute hypobaric hypoxia and its related mechanism.

　　Methods Sixty-four male Sprague-Dawley rats were randomly divided into four groups, including normal group (C), Tongxinluo group (TXL), hypobaric hypoxia group (HH), and hypobaric hypoxia + Tongxinluo group (TXL). +HH). Before hypobaric hypoxia exposure, all rats underwent 5 d water maze training. They were then exposed to a hypobaric and hypoxic environment for 7 d. After 7 days, the cognitive function was measured by open field test and water maze test, and then the hippocampus was sacrificed to detect the expressions of TLR-4, MyD88, IκB-α, NF-κB p65, AQP4, MMP-9 in the hippocampus tissue by Western blot. , ELISA was used to detect the levels of IL-1β, TNF-α, IL-6 in serum and hippocampus, HE staining was used to observe the pathological changes of hippocampus, and the content of brain water in rats was determined.

　　Results (1) Behavioral experiment: There was no statistical difference in the results of the open field experiment among the four groups of rats (P> 0.05); The quadrant stay time and the times of crossing the platform were significantly decreased (P<0.05); after TXL intervention, the stay time in the quadrant and the times of crossing the platform were significantly increased in the lower hypoxic group (P<0.05) (2) Comparison of inflammatory indexes: Compared with group C, the levels of IL-1β, TNF-α, IL-6 in serum and hippocampus, and the levels of TLR-4, MyD88, NF-κB p65 protein in HH group were significantly increased. (P<0.05), after TXL intervention, the levels of inflammatory index-related proteins decreased (P<0.05); (3) Comparison of hippocampal tissue damage: HH group rats hippocampal AQP4 and MMP-9 expression and brain water content Significantly higher than that in group C (P<0.05), the hippocampal cells were arranged disorderly, with obvious swelling and blurred boundaries; and after TXL intervention, the expression of AQP4, MMP-9 and the content of cerebral water were significantly decreased (P<0.05) .

　　Conclusions Acute hypobaric hypoxia exposure can lead to cognitive dysfunction and brain tissue edema. Tongxinluo intervention can reduce hippocampal inflammation and improve cognitive impairment and brain tissue edema by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.