Gastrodin Ameliorates Acute Rejection via IRE1 α/TRAF2/NF- κ B in Rats Receiving Liver Allografts

天麻素通过 IRE1 α/TRAF2/NF- κ B 改善大鼠肝移植急性排斥反应

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作者:Fangchao Yuan, Xuesong Xu, Yakun Wu, Shigang Duan, Hao Wu

Background

Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT.

Conclusion

GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT.

Methods

Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations.

Results

With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P < 0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P < 0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P < 0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P < 0.05).

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