Effects of gut microbiota, GRP78 and TLR4 on the development of liver cirrhosis in rats

doi:10.13418/j.issn.1001-165x.2019.03.004

Chinese Journal of Clinical Anatomy ›› 2019, Vol. 37 ›› Issue (3) : 254-260. DOI: 10.13418/j.issn.1001-165x.2019.03.004

CHEN Yun-xia¹, ZHANG Hui-ying², YANG Ze-xi³, LAI Li-na⁴, MENG Li¹, LI Xu-jiong⁵

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Abstract

Objective 　To study the effects of gut microbiota, glucose-regulated protein 78 (GRP78) and toll-like receptors 4 (TLR4) on the development of liver cirrhosis in rats.　Methods　Thirty-six male SD rats were randomly divided into a normal control group (N) and a hepatic cirrhosis model group (M). The liver cirrhosis was induced by compound factors. Each group was sampled at 4, 6 and 8 week time points. Injuries of liver and intestinal mucosa were assessed with H&E stain. The gut microbiota was examined with automated ribosomal intergenic-spacer analysis (ARISA) on fecal DNA, and the bacterial translocation was assessed by standard microbiological techniques on blood, mesenteric lymph nodes (MLN), ascites and liver. The levels of alanine aminotransferase (ALT), endotoxin and homocysteine (Hcy) in the plasma were detected by enzyme-linked immunosorbent assay (ELISA). The expression of GRP78 and TLR4 was analyzed using quantitative real-time PCR and Western blotting.　Results　Compared to group N, the pathologic change of liver and small intestine was obvious in group M, and the levels of ALT, endotoxin, Hcy in the plasma were significantly and gradually increased. The occurrence of bacterial translocation (BT) was increased in the liver of group M compared to that of group N. BT was not detected in the blood in any group. The expression of GRP78 was significantly and gradually increased in the tissues of liver and ileum in group M. In liver homogenate, the expression of TLR4 in group M was significantly and gradually increased in 6 weeks, and significantly higher than group N at 8 weeks, but lower than group M at 6 weeks. In ileal homogenate, the expression of TLR4 in group M was also significantly and gradually increased in 6 weeks, but was significantly decreased than group N at 8 weeks.　Conclusion　With the progress of liver cirrhosis, the dysbiosis of gut microbiota becomes more and more serious, the expression of GRP78 increases significantly and the expression level of TLR4 decreases significantly in ileal homogenate, which may result in the gradual increase of the intestinal mucosal barrier damage, and cause significant increase of the occurrence of BT and level of endotoxin, eventually affecting the expression of GRP78 and TLR4 in liver, and worsening liver injury then.

Key words

Hepatic cirrhosis / 　Gut microbiota / 　Bacterial translocation / 　GRP78 / 　TLR4

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CHEN Yun-xia, ZHANG Hui-ying, YANG Ze-xi, LAI Li-na, MENG Li, LI Xu-jiong. Effects of gut microbiota, GRP78 and TLR4 on the development of liver cirrhosis in rats[J]. Chinese Journal of Clinical Anatomy. 2019, 37(3): 254-260 https://doi.org/10.13418/j.issn.1001-165x.2019.03.004

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