| 引用本文: | 韦文香,熊伟,游婧璨,陈光友,刘艳.黄连素通过对高脂小鼠肝脏、胰腺中PCSK9和LDLR的不同调控改善高脂血症和高胰岛素血症[J].中国现代应用药学,2022,39(14):1803-1807. |
| WEI Wenxiang,XIONG Wei,YOU Jingcan,CHEN Guangyou,LIU Yan.Berberine Attenuates Hyperlipidemia and Hyperinsulinemia in Mice Fed with High-Fat Diet in Associated with Differential Regulation of PCSK9 and LDLR in Liver and Pancreas[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(14):1803-1807. |
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| 摘要: |
| 目的 观察黄连素对高脂小鼠肝脏、胰腺中PCSK9和LDLR的不同调控，探讨其减缓高脂血症和高胰岛素血症的新作用机制。方法 SPF级C57BL/6J小鼠随机分为3组：正常对照组(普通饮食喂养)、高脂饲料组(高脂饮食喂养)、黄连素组(高脂饮食喂养同时灌胃黄连素)。自动血糖仪检测空腹血糖值；酶联免疫法(ELISA)测空腹血清胰岛素水平，计算血糖与胰岛素比值。ELISA测空腹血清PCSK9水平；酶标仪和相应的试剂盒检测血清中的甘油三酯、总胆固醇、高密度胆固醇、低密度胆固醇的含量。HE染色法观察肝脏和胰腺的组织形态变化。Western blotting检测肝脏和胰腺中PCSK9和LDLR蛋白的表达。结果 黄连素能降低血清中胆固醇的含量，同时明显降低血浆中PCSK9的含量，减少肝脏PCSK9蛋白表达，增加肝脏表面LDLR蛋白表达；改善高脂诱导的胰岛素抵抗，减少胰岛细胞肥大及空泡数量，增加胰腺表面PCSK9蛋白表达，减少胰腺表面LDLR蛋白表达。结论 黄连素调节高脂饮食小鼠PCSK9的表达和分泌，具有组织特异性，在肝脏中增强LDLR介导的胆固醇细胞摄取，同时在胰腺中抑制LDLR介导的胆固醇摄取，从而改善高脂饮食诱导的肝脏脂肪性病变和胰岛素抵抗。 |
| 关键词: 黄连素 PCSK9 肝脏 胰腺 LDLR |
| DOI：10.13748/j.cnki.issn1007-7693.2022.14.003 |
| 分类号:R285.5 |
| 基金项目:四川省科技计划项目(2018SZ0406)；泸州市人民政府-西南医科大学科技战略合作项目(2019LZXNYDJ51)；西南医科大学校级大创项目(2021426，2021502) |
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| Berberine Attenuates Hyperlipidemia and Hyperinsulinemia in Mice Fed with High-Fat Diet in Associated with Differential Regulation of PCSK9 and LDLR in Liver and Pancreas |
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WEI Wenxiang1, XIONG Wei2, YOU Jingcan1, CHEN Guangyou3, LIU Yan1
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1.Southwest Medical University, Drug Discovery Research Center, Luzhou 646000, China;2.Southwest Medical University, Department of Science and Technology, Luzhou 646000, China;3.Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
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| Abstract: |
| OBJECTIVE To observe the differential regulation of berberine on PCSK9 and LDLR in liver and pancreas of hyperlipidemia mice, and to explore the new effect and mechanism of berberine on reducing hyperlipidemia and hyperinsulinemia. METHODS SPF grade C57BL/6J mice were randomly divided into 3 groups. The control group was fed with normal diet, the high fat diet group was fed with high fat diet, and the berberine group was given both high fat diet and berberine by gastric perfusion at the same time. Fasting blood glucose was measured by automatic glucose meter. Fasting serum insulin was measured by enzyme-linked immunosorbent assay(ELISA), and the ratio of blood glucose to insulin was calculated. Fasting serum PCSK9 level was measured by ELISA. The contents of triglyceride, total cholesterol, high density cholesterol and low density cholesterol in serum were determined by ELISA and corresponding kit. The morphological changes of liver and pancreas were observed by HE staining. The expressions of PCSK9 and LDLR proteins in liver and pancreas were detected by Western blotting. RESULTS Berberine could reduce cholesterol content in serum, PCSK9 content in plasma, PCSK9 protein expression of liver, and increase LDLR protein expression on liver surface. It could improve insulin resistance induced by high fat diet, reduce the number of hypertrophy and vacuoles of islet cells, increase the expression of PCSK9 protein on pancreatic surface, and decrease the expression of LDLR protein on pancreatic surface. CONCLUSION Berberine regulates the expression and secretion of PCSK9 in high fat diet mice with tissue specificity, enhance LDLR-mediated cholesterol cell uptake in liver and inhibiting LDLR-mediated cholesterol uptake in pancreas, thereby improving liver fatty disease and insulin resistance induced by high fat diet. |
| Key words: berberine PCSK9 liver pancreas LDLR |
