Zhang L, Gao X F, Wang Y H
Department of Cardiovascular and Thoracic Surgery, Taiyuan Central Hospital, Taiyuan 030006, China.
Zhonghua Yi Xue Za Zhi. 2018 Aug 14;98(30):2407-2413. doi: 10.3760/cma.j.issn.0376-2491.2018.30.008.
To study the role of chemerin in the development and progression of non-alcoholic fatty liver disease (NAFLD) rats complicated with prediabetes and explore the effect of sitagliptin on the expression of chemerin. The model of NAFLD and prediabetic rats was established. The rats were then randomly divided into normal group, model group and intervention group. Sitagliptin intervention was performed for 8 weeks after 8 weeks's feeding with high-fat diet. After that, the level of blood glucose, insulin and chemerin was measured. Cytological changes of liver, omentum and epididymal adipose tissue were observed by HE staining. The distribution of chemerin in the tissues was observed by immunohistochemistry. The mRNA and protein expression of chemerin and chemokine-like receptor 1 (chemR23) in liver and adipose tissue were detected by RT-PCR and Western blotting. After 8 weeks of sitagliptin treatment, compared with the normal group(=8), serum chemerin in the model group (=6) increased[(35.19±3.86) ng/L vs (29.90±2.17) ng/L, =0.046)]. Serum chemerin in the intervention group (=6) was lower than that of the normal group[(23.20±1.89) ng/L vs (29.90±2.17) ng/L, =0.013)]. Compared with the normal group, the mRNA and protein expression of chemerin in the liver and omentum adipose tissue of the model group increased (<0.05). The expression amount of the omental adipose tissue was more than that of the liver(<0.05). The mRNA expression of chemR23 both in liver and omental adipose tissue increased (<0.05), and the expression amount of the liver was more than that of omental adipose tissue. The levels of fasting blood glucose[(5.72 ±1.36)mmol/L vs(3.77±0.77)mmol/L, =0.002], total cholesterol[(1.53±0.09)mmol/L vs (1.23±0.17)mmol/L, =0.032], aspartate aminotransferase[(319.8±104.4)U/L vs (195.0±25.0) U/L, =0.016]in the model group were significantly higher than those in the normal group. The differences between the intervention group and the normal group was not significant. But the level of fasting blood glucose[(4.33±0.39)mmol/L vs (5.72±1.36)mmol/L, =0.019], total cholesterol[(1.23±0.17)mmol/L vs (1.53±0.09)mmol/L, =0.047]and aspartate aminotransferase[(198.4±22.8)U/L vs (319.8±104.4)U/L, =0.014)]of the intervention group was significantly lower than those of the model group. Increasing expression of serum chemerin is consistent with hepatic steatosis, suggesting that chemerin can serve as a serological warning indicator for NAFLD complicated with pre-diabetes. Sitagliptin affects the mRNA and protein expression of chemerin and its receptor chemR23 in steatosis liver. This may provide a research direction for the pathophysiology and treatment of NAFLD.
研究趋化素在非酒精性脂肪性肝病（NAFLD）合并糖尿病前期大鼠发生发展中的作用，并探讨西他列汀对趋化素表达的影响。建立NAFLD合并糖尿病前期大鼠模型，然后将大鼠随机分为正常组、模型组和干预组。高脂饮食喂养8周后，对干预组进行西他列汀干预8周。之后，检测血糖、胰岛素和趋化素水平。通过HE染色观察肝脏、网膜和附睾脂肪组织的细胞学变化。通过免疫组织化学观察趋化素在组织中的分布。采用RT-PCR和Western blotting检测肝脏和脂肪组织中趋化素和趋化因子样受体1（chemR23）的mRNA和蛋白表达。西他列汀治疗8周后，与正常组（n = 8）相比，模型组（n = 6）血清趋化素升高[（35.19±3.86）ng/L vs（29.90±2.17）ng/L，P = 0.046]。干预组（n = 6）血清趋化素低于正常组[（23.20±1.89）ng/L vs（29.90±2.17）ng/L，P = 0.013]。与正常组相比，模型组肝脏和网膜脂肪组织中趋化素的mRNA和蛋白表达增加（P < 0.05）。网膜脂肪组织中的表达量高于肝脏（P < 0.05）。肝脏和网膜脂肪组织中chemR23的mRNA表达均增加（P < 0.05），且肝脏中的表达量高于网膜脂肪组织。模型组空腹血糖[（5.72 ±1.36）mmol/L vs（3.77±0.77）mmol/L，P = 0.002]、总胆固醇[（1.53±0.09）mmol/L vs（1.23±0.17）mmol/L，P = 0.032]、天冬氨酸转氨酶[（319.8±104.4）U/L vs（195.0±25.0） U/L，P = 0.016]水平显著高于正常组。干预组与正常组之间差异不显著。但干预组空腹血糖[（4.33±0.39）mmol/L vs（5.72±1.36）mmol/L，P = 0.019]、总胆固醇[（1.23±0.17）mmol/L vs（1.53±0.09）mmol/L，P = 0.047]和天冬氨酸转氨酶[（198.4±22.8）U/L vs（319.8±104.4）U/L，P = 0.014]水平显著低于模型组。血清趋化素表达增加与肝脂肪变性一致，提示趋化素可作为NAFLD合并糖尿病前期的血清学警示指标。西他列汀影响脂肪变性肝脏中趋化素及其受体chemR23的mRNA和蛋白表达。这可能为NAFLD的病理生理学和治疗提供一个研究方向。
