[Animal Modeling]-Effect of Tongxinluo Capsule on Inflammatory Response, Brain Edema and Cognitive Function after Exposure to Low Pressure and Hypoxia in Rats

  Objective: To investigate the neuroprotective effect of Tongxinluo Capsule on cognitive impairment in rats with acute hypoxia and its related mechanisms.

  Method: 64 male Sprague-Dawley rats were randomly divided into 4 groups: normal group (C), Tongxinluo group (TXL), hypobaric hypoxia group (HH) and hypobaric hypoxia + Tongxinluo group. (TXL + HH). All rats were trained in a water maze for 5 days before being exposed to low pressure and hypoxia. It was then exposed to low pressure and hypoxia for 7 days. Seven days later, open field and water maze experiments were used to determine cognitive function, and then hippocampal tissue was harvested at the expense of hippocampal tissue. Western blot was used to detect the expression of TLR-4, MyD88, and IκB-. Hippocampus α, NF-κBp65, AQP4 and MMP-9. The levels of IL-1β, TNF-α and IL-6 in serum and hippocampus tissue. HE staining to observe the pathological changes of hippocampus. Measure the brain water content of rats.

  Results: (1) Behavior experiment: There was no statistical difference in the results of the four groups of rats in the field experiment (P→0.05); but in the water maze space exploration experiment, compared with the C group, the original HH group's platform was: The time spent in the quadrant and the number of passes through the platform has been significantly reduced (Pu003c0.05). After TXL intervention, the time of placing the quadrant in the original platform and passing through the platform in the hypothalamus group was significantly reduced (Pu003c0.05); (2) Inflammation index comparison: NF-κB p65 serum and hippocampal tissue IL-1β and TNF-α in group C The protein levels in the, IL-6, hippocampal TLR-4, MyD88 and HH groups increased significantly (Pu003c0.05). Inflammation index-related proteins decreased (Pu003c0.05); (3) Hippocampal tissue damage comparison: HH group rat hippocampal AQP4 and MMP-9 expression and brain water content C were significantly higher than the group (Pu003c0.05). 05)), the hippocampal cells are arranged randomly, with obvious swelling and blurred boundaries; after TXL intervention, the expression of AQP4, MMP-9 and brain water content was significantly reduced (Pu003c0.05).

  Conclusion: Acute hypobaric hypoxia exposure can cause cognitive dysfunction and cerebral edema. Tongxinluo intervention inhibits the activation of TLR4/MyD88/NF-κB signaling pathway, reduces hippocampal inflammation, and improves cognitive impairment and cerebral edema.