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金钗石斛多糖调控炎性小体NLRP3对非酒精性脂肪肝大鼠的保护作用

2021-06-24范艳喻涓杨榆青何丹姚政宋波

世界中医药 2021年4期
关键词:剂量模型

范艳 喻涓 杨榆青 何丹 姚政 宋波

摘要 目的:研究金釵石斛多糖对NAFLD大鼠的干预作用,并从NLRP3信号通路分析作用机制。方法:将72只SD大鼠分为正常、模型、金钗石斛多糖高、中、低剂量和多烯磷脂酰胆碱干预组,除正常组外,NAFLD模型构建成功治疗4周后处死,取出肝脏检测肝脏病理学和NLRP3、Caspase-1蛋白及mRNA表达,收集血液检测谷草转氨酶(AST)、谷丙转氨酶(ALT)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)含量。结果:正常组肝小叶清晰,细胞核分布均匀,模型组有明显脂肪空泡和炎症反应浸润,金钗石斛多糖与多烯磷脂酰胆碱组明显改善;与正常组比较,模型组AST、ALT、TG、TC、HDL-C、LDL-C、IL-1β、IL-18、Caspase-1和NLRP3蛋白及mRNA均升高(P<0.05),与模型组比较,金钗石斛多糖组和多烯磷脂酰胆碱组上述指标均降低(P<0.05),此外金钗石斛多糖组与多烯磷脂酰胆碱组AST、ALT和HDL-C没有差异,高剂量组TG、TC和LDL-C低于多烯磷脂酰胆碱组(P<0.05),中和高剂量组IL-1β、IL-18、Caspase-1和NLRP3蛋白及mRNA明显低于多烯磷脂酰胆碱组(P<0.05)。结论:金钗石斛多糖可明显改善高脂高糖饮食诱导的NAFLD大鼠肝功能和血脂,这与其可调节炎性小体NLRP3,进而降低炎症反应有关。

关键词 金钗石斛多糖;非酒精性脂肪肝;大鼠;血脂;炎症介质;炎性小体;NOD样受体蛋白3;半胱氨酸天冬氨酸蛋白酶

Protective Effects of Dendrobium Nobile Polysaccharide on NLRP3 in Rats with Nonalcoholic Fatty Liver Disease

FAN Yan1,2,YU Juan3,YANG Yuqing2,HE Dan2,YAO Zheng2,SONG Bo2

(1 School of Basic Medicine,Kunming Medical University,Kunming 650500,China; 2 School of Basic Medicine,Yunnan University of Chinese Medicine,Kunming 650504,China; 3 School Hospital,Yunnan Normal University,Kunming 650500,China)

Abstract Objective:To investigate the intervention effect of Dendrobium nobile polysaccharides on NAFLD rats,and to analyze the mechanism of action from the NLRP3 signaling pathway.Methods:A total of 72 SD rats were divided into 6 groups,which were the normal,model,high dose,medium dose,low dose Dendrobium nobile polysaccharide,and the polyene phosphatidylcholine intervention group.Except for the normal group,the other 5 groups were constructed an animal model of NAFLD and after treatment,the rats were sacrificed.Their liver was taken out to detect liver pathology and NLRP3,Caspase-1 protein and mRNA expression.Their blood was also collected to detect the AST,ALT,TG,TC,LDL-C,HDL-C,IL-1β and IL-18.Results:The liver lobules in the normal group were clear,and the nuclei were evenly distributed.The model group had obvious fatty vacuoles and inflammatory reaction infiltration.The Dendrobium nobile polysaccharide and polyene phosphatidylcholine group improved significantly.Compared with the control group,AST,ALT,TG,TC,HDL-C,LDL-C,IL-1β,IL-18,Caspase-1 and NLRP3 protein and mRNA were significantly increased in the model group(P<0.05).Compared with the model group,those indexes in the Dendrobium nobile polysaccharide and the polyene phosphatidylcholine group were significantly lower(P<0.05).In addition,there was no difference in AST,ALT and HDL-C between the Dendrobium nobile polysaccharide group and the polyene phosphatidylcholine group.TG,TC and LDL-C of the high-dose group were lower than those of the polyene phosphatidylcholine group(P<0.05).The protein and mRNA of IL-1β,IL-18,Caspase-1 and NLRP3 in the high-dose group were significantly lower than those in the polyene phosphatidylcholine group(P<0.05).Conclusion:Dendrobium nobile polysaccharides can significantly improve the liver function and blood lipids of NAFLD rats induced by a high-fat and high-sugar diet,which is related to its ability to regulate the inflammasome NLRP3,thereby reducing the inflammatory response.

Keywords Dendrobium nobile polysaccharide; Nonalcoholic fatty liver disease; Rat; Blood lipids; Inflammatory factors; Inflammasome; Nod-like receptor protein-3(NLRP3); Caspase-1

中图分类号:R285.5文献标识码:Adoi:10.3969/j.issn.1673-7202.2021.04.007

有研究显示,当前非酒精性脂肪肝(Nonalcoholic Fatty Liver Disease,NAFLD)在我国发病率逐年升高,目前国内约有1.5亿NAFLD患者,已经超过病毒性肝病,成为发病率最高的肝脏疾病[1]。NAFLD病理学主要表现为肝脏过度脂肪蓄积,进而引起肝细胞实质脂肪变性[2]。本病发生后需积极控制,若控制不佳,有很大概率可随病情进展发展为脂肪性肝炎、肝纤维化、肝硬化甚至肝功能衰竭或肝癌等[3]。因此对本病的积极防治特别重要。目前临床中对于本病的治疗,西药以降糖、降脂和提高抗氧化能力以及消炎为主[4],但治疗效果欠佳。金钗石斛多糖是中药金钗石斛最主要的有效药……

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