Protective Mechanisms of Rapamycin on Intestinal Fibrosis in Chronic Radiation Intestinal Injury
Objective To observe the progression of intestinal fibrosis in chronic radiation intestinal injury(CRII)and study the protective mechanisms of autophagy agonist rapamycin on intestinal fibrosis in CRII.Methods Thirty C57/B6male mice were randomly divided into the control group(CO group),the radiation group(SR group)and the rapamycin intervention group(RI group).The CO group was not treated.In SR group,the CRII model(single dose of9Gy radiation)was established first,and the samples were taken after 3months.In RI group,the rats were treated with rapamycin(2mg/kg,intraperitoneal injection)for 1 week after modeling,other treat-ments were the same as that in SR group.Hematoxylin-eosin staining and Masson staining were used to evaluate the degree of intestinal mucosal injury and intestinal fibrosis.Enzyme-linked immunosorbent assay was used to detect the serum levels of interleukin-1 β(IL-1β)and interleukin-6(IL-6).The level of intestinal α-smooth muscle actin(α-SMA)was detected by immunohistochemistry.The levels of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF)and autophagy-related proteins(p62 and LC3)were detected by Western blot.Results Histopathological staining showed that compared with CO group,the intestinal muco-sal damage was aggravated(P＜0.05),and the degree of intestinal fibrosis was increased in SR group(P＜0.01).Compared with SR group,the intestinal mucosal damages were relieved(P＜0.05),and the intestinal fibrosis was greatly decreased in RI group(P＜0.01).Compared with the CO group,the levels of IL-1 β and IL-6 in the SR group were significantly increased(P＜0.01),while those in the RI group significantly decreased compared with the SR group(P＜0.01).The results of immunohistochemistry and Western blot showed that the expression levels of α-SMA,TGF-β1 and CTGF in the SR group were greatly higher than those in the CO group(P＜0.05),while significantly lower in the RI group than those in the SR group(P＜0.05).The expression of autophagy indexes in SR group were lower than that in the CO group(P＜0.05),and significantly higher in the RI group than that in the SR group(P＜0.05).Conclusion Rapamycin-induced autophagy could improve the process of intestinal fibrosis in CRII,and the mechanism may be related to the inhibition the differentiation and function of intestinal myofibroblasts and reduce the inflammation of intestine.
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