Effect of glutaminase 1 inhibitor on carbon tetrachloride-induced liver fibrosis in mice
Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-(5-phenylaceta-mido-1,3,4-thiadiazol-2-yl)ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10％CC14(10 μL/g,model group)or 10％CC14(10 µL/g)+BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model.Collagen deposition in mouse liver tissue was observed by Sirius red staining.The expression levels of actin alpha 2(Acta2),collagen type Ⅰ alpha 1(Collαl)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t=2.979,P＜0.05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t=7.661,P＜0.01),the relative expression levels of Acta2 and Col1α1 significantly increased(t=4.335 and 5.319,respectively,each P＜0.01),and the mRNA and protein levels of GLS1 significantly increased(t=5.319 and 9.725,respectively,each P＜0.01).However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t=7.427,P＜0.01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t=3.713 and 2.628,respectively,each P＜0.05).Conclusion Inhibition of GLS1 activity can significantly improve the degree of liver fibrosis induced by CC14,providing a new idea for the treatment of liver fibrosis.
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