升陷化纤方及拆方通过ATF4/CHOP通路抑制M2巨噬细胞极化抗大鼠肺纤维化的机制研究OA

Objective To compare the effects of Shengxian Huaxian Recipe and its disassembled prescriptions in the treatment of pulmonary fibrosis,and to explore the possible mechanism of its prevention and treatment of pulmonary fibrosis.Methods Seventy male SD rats were randomly divided into 7 groups:the blank group,the model group,the positive group(pirfenidone,0.12 g/kg),the Shengxian Huaxian group(12.60 g/kg),the Shengxian group(7.65 g/kg),the Tongluo group(3.60 g/kg),and the Bushen group(2.25 g/kg),with 10 rats in each group.Except for the blank group,the other groups were used to prepare the pulmonary fibrosis model by intratracheal instillation of bleomycin(5 mg/kg).After model establishment,the rats were allowed to acclimate for one week.Subsequently,the blank group and the model group were intragastrically administered the same volume of normal saline,while the other groups were intragastrically administered the corresponding drugs once a day for 28 consecutive days.The general condition of the rats and the pathological morphological changes of the lung tissue were observed;the expressions of CD206,CD163,CD68,and iNOS were detected by immunohistochemistry;the expressions of ATF4,CHOP,P-eIF2α,α-SMA,and E-cadherin proteins were detected by Western blot;and the mRNA expression levels of CHOP,ATF4,and eIF2α were detected by RT-qPCR.Results Compared with the blank group,the model group showed the following changes:the pathological manifestations were the destruction and atrophy of alveolar tissue,the widening of alveolar septum,the damage of tracheal structure,the infiltration of a large number of inflammatory cells in the alveolar cavity and tracheal cavity,and the deposition of a large number of blue collagen fibers;the expression of CD206 and CD163 in lung tissue was increased(P<0.01),and the expression of CD68 and iNOS was not statistically different(P>0.05);the expression of ATF4,CHOP,P-eIF2α,α-SMA protein was up-regulated,and E-cadherin protein was down-regulated(P<0.01);the mRNA expression levels of CHOP,ATF4 and eIF2α were increased(P<0.01).Compared with the model group,all administration groups showed the following changes:the pathological damage of lung tissue was improved;the expressions of CD206 and CD163 were decreased(P<0.01);the expressions of CD68 and iNOS were increased(P<0.01);the expressions of ATF4,CHOP,P-eIF2α and α-SMA were decreased,and the expression of E-cadherin was increased(P<0.05);and the mRNA expression levels of CHOP,ATF4 and eIF2α was decreased(P<0.01).The Shengxian Huaxian group demonstrated the most significant improvement,followed by the Shengxian group.Conclusion The effect of Shengxian Huaxian Recipe and its disassembled prescriptions on pulmonary fibrosis is the best in Quanfang group of Shengxian Huaxian Recipe.In the disassembled prescription group,the effect of Shengxian group is better than that of Tongluo group and Bushen group.The mechanism may be related to the inhibition of M2 macrophage polarization through endoplasmic reticulum stress ATF4/CHOP pathway.