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CHEN Songtao^1ab, YIN Kai² , HE Qingzhi^1ab, ZHU Xiao^1a

( 1. a. Guangxi Key Laboratory of Diabetes System Medicine, b. College of Intelligent Medicine andBiotechnology, Guilin Medical University, Guilin 541199, China ;2. General Practice ,the Fifth Afiliated Hospital of Southem Medical University, Guangzhou 510920, China)

Abstract0bjective 'To explore the expression changes of activated transcription factor 4 ( ATF4) and its effect onthe oecurrenee and development of intestinal inflammation in type 2 diabetes ('T2D ). Methods Streptozotoein( STZ)combined with high-fat diet was used to construct a mouse model of 'T2D. The protein expression level of A'TF4 inintestinal tissues of mice was detected by Wester Blot ( WB ) and immunohistochemistry ( lHC ). The pathologicalchange of intestinal tissue was observed by hematoxylin-eosin ( HE ) staining. Real-time quantitative PCR ( qR'T.PCR ) was used to detect the levels of inflammatory factors in the intestinal tissues of mice. Gaco-2 cells were treatedwith high-concentration glucose medium to simulate the hyperglycemic state, and the protein expression level olA'TF4 in the cells was detected by WB and immunoluorescence ( IF). Caco-2 cells were transfected with ATF4overexpression plasmid, and the protein expression level of A'T'F4 was detected by WB. 'T'he level of inflammatory wasdetected by qR'T-PCR, Results Compared with normal mice, ATF4 protein expression in intestinal tissues of diabeticmice was significantly down-regulated, and the intestinal tissue showed significant pathologic changes, such asthinning of intestinal wall and sparse goblet cells. The levels of inflammatory factors in intestinal tissues of diabeticmice were significantly inereased compared with those in normal mice, the difference is stootistically significant( P<0.05 ). Compared with normal group , the protein expression of A'TF4 in Caco-2 cells was significantly down-regulatedafter high glucose treatment( P<0.05 ). The levels of inflammatory factors in Caco-2 cells were significantly increasedcompared with those in normal group. Overexpression of ATF4 reversed the expression levels of inflammatory factorsin cells indueed by high glucose environment( P<0.05). Conclusion Hyperglycemia may promote intestinalinflammatory response in T2D by inhibiting the expression of intestinal ATF4.

Keywords : type 2 diabetes ; hyperglyeemia ; activated transcription factor 4; intestinal inflammation

DOI:10.19296/j.cnki.1008-2409.2024-02-002

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