艾灸对克罗恩病大鼠结肠H3K27乙酰化的调节作用研究OA

Objective:To investigate the regulatory effect of moxibustion on rats with Crohn disease(CD)and explore the relationship between the effect and alterations in colonic histone H3 lysine 27 acetylation(H3K27ac). Methods:Ten out of 36 Sprague-Dawley rats were randomly selected as the control group using a random number table method.The remaining 26 rats received an enema of 2,4,6-trinitrobenzene sulfonic acid to establish a CD model.Successfully modeled rats were then randomly divided into a model group,an herb-insulated moxibustion group,and a sulfasalazine group using the random number table method,with 8 rats in each group.The herb-insulated moxibustion group received herb-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),and the sulfasalazine group received sulfasalazine via gavage.Histopathological changes in the colonic tissues were assessed using hematoxylin-eosin staining.The serum levels of inflammatory factors[tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6]were measured using the enzyme-linked immunosorbent assay.The protein expression of colonic H3K27ac was detected using Western blotting and immunohistochemistry.The mRNA and protein expression levels of K-acetyltransferase 2B(KAT2B),general control non-repressed protein 5(GCN5),histone deacetylase 1(HDAC1),and histone deacetylase 3(HDAC3)in the colon were determined using real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence,respectively. Results:Compared to the control group,the histopathological score,serum levels of TNF-α,IL-1β,and IL-6,and the mRNA and protein expression of GCN5,HDAC1,and HDAC3 in the colon were significantly increased in the model group(P<0.01 or P<0.05),whereas the protein expression of H3K27ac and the mRNA and protein expression of KAT2B were significantly decreased in the model group(P<0.01 or P<0.05).In contrast,compared to the model group,the histopathological score,serum levels of TNF-α,IL-1β,and IL-6,and the mRNA and protein expression of GCN5,HDAC1,and HDAC3 in the colon were significantly decreased in the herb-insulated moxibustion group(P<0.01 or P<0.05),whereas the protein expression of H3K27ac and the mRNA and protein expression of KAT2B were significantly increased in the model group(P<0.01 or P<0.05).No significant differences in the aforementioned indicators were observed between the sulfasalazine group and the herb-insulated moxibustion group. Conclusion:Moxibustion alleviates colonic inflammation in CD rats,potentially by up-regulating the expression of KAT2B,down-regulating the expression of GCN5,HDAC1,and HDAC3,and consequently increasing the H3K27ac level.