Abstract: Objective: To observe the role of calcium sensitive receptor (CaSR) in the pathogenesis of diabetic liver injury. Methods: Forty Wistar rats were randomly divided into normal control group (control, n=10) and diabetes group (T1D, STZ 60 mg/kg intraperitoneal injection, n=30), and the samples were collected at the 2nd, 4th and 8th week. Rats hepatic stellate cells (HSC) were randomly divided into normal control group (Control, 10% FBS-DMEM culture, n=5), high glucose group (HG, 10% FBS-DMEM+40 mmol/L glucose, treated for 48 h, n=5) and CaSR inhibitor group (HG+Calhex 231, 10% FBS-DMEM+40 mmol/L glucose+2.5 μmol/L Calhex₂₃₁ for 48h, n=5). The body weight, blood glucose, serum glutamic oxaloacetic transaminase (AST) and alanine aminotransferase (ALT) activities were measured dynamically. The changes of liver morphology and ultrastructure were observed by HE staining and Masson staining by transmission electron microscopy. The changes of CaSR and liver fibrosis related indexes were detected by Western blot.Results: Compared with the control group, diabetic rats lost weight, while blood glucose, AST and ALT increased significantly, and the expression of CaSR, collagen Ⅰ(CO Ⅰ), collagen Ⅲ (CO Ⅲ), matrix metalloproteinase(MMP)-1, -2 and -9 increased significantly. The results of the cell model were basically the same as those in vivo. Compared with the control group, the expression of α-smooth muscle actin (α-SMA) was increased, indicating that HSC differentiated into myofibroblasts in HG group. The expression of the main components of ECM (CO Ⅰ and CO Ⅲ), and the key enzyme of ECM degradation (MMP9) were also increased, while CaSR inhibitor, Calhex₂₃₁, could reduce the above changes.Conclusion: The up-regulation of CaSR expression is involved in the occurrence of diabetic liver injury and fibrosis.

Key words: diabetes mellitus, liver fibrosis, calcium-sensing receptor (CaSR), rats