茵陈蒿汤对NAFLD伴IR大鼠的肝保护作用及其机制
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摘要
目的探讨茵陈蒿汤对非酒精性脂肪肝(NAFLD)伴胰岛素抵抗(IR)大鼠的肝保护作用及其作用机制。方法选择SD大鼠120只,随机分为对照组、模型组、辛伐他汀组及茵陈蒿汤低、中、高剂量组,每组20只。模型组、辛伐他汀组及茵陈蒿汤低、中、高剂量组给予普通饲料+10%果糖水喂养6周,建立NAFLD伴IR模型;第7周开始,模型组给予蒸馏水10 mL/kg灌胃,辛伐他汀组给予辛伐他汀200 mg/kg灌胃,茵陈蒿汤低、中、高剂量组分别给予茵陈蒿汤20、30、40 g/kg灌胃,连续4周,期间继续普通饲料+10%果糖水喂养。对照组普通饲料+蒸馏水喂养。末次灌胃结束,眶后静脉丛取血,检测肝损伤指标、脂肪肝病变指标、糖脂代谢指标、肝脏纤维化指标及脂肪因子指标。禁食12 h,脱臼处死,快速分离肝组织,肉眼观察肝组织形态学改变,计算肝脏系数。取部分肝组织,分别行HE、Masson染色,评估肝组织病理学评分和纤维化程度评分。结果茵陈蒿汤各剂量组能明显改善NAFLD伴IR大鼠肝损伤指标、脂肪肝病变指标及糖脂代谢指标,还能改善肝纤维化指标和脂肪因子水平,降低肝脏系数和肝纤维化程度,改善肝组织病理变化;这些作用具有一定量效关系,在一定范围内茵陈蒿汤剂量越大,上述效果越明显,茵陈蒿汤高剂量组效果甚至与辛伐他汀组相当。结论茵陈蒿汤能够剂量依赖性地改善NAFLD伴IR大鼠糖脂代谢,进而减轻肝脏脂肪病变,缓解肝纤维化程度;其机制可能与调节脂肪因子水平、降低IR、改善糖脂代谢紊乱,从而逆转肝细胞损伤有关。
Objective To investigate the protective effect and mechanism of Yinchenhao decoction on the liver of rats with non-alcoholic fatty liver disease(NAFLD) and insulin resistance(IR).Methods Totally 120 SD rats were randomly divided into the control group, model group, simvastatin group and low-dose, medium-dose, and high-dose Yinchenhao decoction groups, with 20 rats in each group. The rats in the model group, simvastatin group and low-dose, medium-dose and high-dose Yinchenhao decoction groups were fed with normal diet plus 10% fructose water for 6 weeks to establish NAFLD models with IR. From the 7 th week, the rats in the model group were given 10 mL/kg distilled water by gavage, the simvastatin group was given 200 mg/kg simvastatin by gavage, and the low-dose, medium-dose and high-dose Yinchenhao decoction groups were given 20, 30, 40 g/kg Yinchenhao decoction by gavage, respectively, for 4 consecutive weeks, during which normal diet and 10% fructose water was continued to be fed. The control group was fed with normal diet and distilled water. At the end of the last gastric lavage, blood was collected from the posterior orbital venous plexus. Liver injury index, fatty liver disease index, glycolipid metabolism index, liver fibrosis index, and adipokine index were detected. Rats were fasting for 12 h, and then were dislocated and killed. Liver tissues were separated quickly. The morphological change of liver tissues was observed with naked eyes, and the liver coefficient was calculated. Some liver tissues were taken out, and HE staining and Masson staining was performed to evaluate the pathological score and fibrosis degree of liver tissue.Results Yinchenhao decoction could significantly improve the liver injury index, fatty liver disease index and glycolipid metabolism index of NAFDL rats with IR. It could also improve the liver fibrosis index and adipokine level, reduce the liver coefficient and the degree of liver fibrosis, and improve the pathological changes of liver tissue, with a dose-effect relationship, and the higher the Yinchenhao decoction dosage in a certain range, the more significant the above effects would become. The effect of the high dose Yinchenhao decoction group was even similar to that of the simvastatin group.Conclusions Yinchenhao decoction can improve glycolipid metabolism in rats with NAFDL and IR in a dose-dependent manner, thereby alleviating hepatic steatosis and liver fibrosis. Its mechanism may be related to regulating the level of adipokines, reducing insulin resistance, improving the disorder of glycolipid metabolism, and affecting the changes of inflammatory factors to reverse hepatocyte injury.
Objective To investigate the protective effect and mechanism of Yinchenhao decoction on the liver of rats with non-alcoholic fatty liver disease(NAFLD) and insulin resistance(IR).Methods Totally 120 SD rats were randomly divided into the control group, model group, simvastatin group and low-dose, medium-dose, and high-dose Yinchenhao decoction groups, with 20 rats in each group. The rats in the model group, simvastatin group and low-dose, medium-dose and high-dose Yinchenhao decoction groups were fed with normal diet plus 10% fructose water for 6 weeks to establish NAFLD models with IR. From the 7 th week, the rats in the model group were given 10 mL/kg distilled water by gavage, the simvastatin group was given 200 mg/kg simvastatin by gavage, and the low-dose, medium-dose and high-dose Yinchenhao decoction groups were given 20, 30, 40 g/kg Yinchenhao decoction by gavage, respectively, for 4 consecutive weeks, during which normal diet and 10% fructose water was continued to be fed. The control group was fed with normal diet and distilled water. At the end of the last gastric lavage, blood was collected from the posterior orbital venous plexus. Liver injury index, fatty liver disease index, glycolipid metabolism index, liver fibrosis index, and adipokine index were detected. Rats were fasting for 12 h, and then were dislocated and killed. Liver tissues were separated quickly. The morphological change of liver tissues was observed with naked eyes, and the liver coefficient was calculated. Some liver tissues were taken out, and HE staining and Masson staining was performed to evaluate the pathological score and fibrosis degree of liver tissue.Results Yinchenhao decoction could significantly improve the liver injury index, fatty liver disease index and glycolipid metabolism index of NAFDL rats with IR. It could also improve the liver fibrosis index and adipokine level, reduce the liver coefficient and the degree of liver fibrosis, and improve the pathological changes of liver tissue, with a dose-effect relationship, and the higher the Yinchenhao decoction dosage in a certain range, the more significant the above effects would become. The effect of the high dose Yinchenhao decoction group was even similar to that of the simvastatin group.Conclusions Yinchenhao decoction can improve glycolipid metabolism in rats with NAFDL and IR in a dose-dependent manner, thereby alleviating hepatic steatosis and liver fibrosis. Its mechanism may be related to regulating the level of adipokines, reducing insulin resistance, improving the disorder of glycolipid metabolism, and affecting the changes of inflammatory factors to reverse hepatocyte injury.
引文
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[15] 陈梅,宋爱华,程雪娟,等.非酒精性脂肪肝发病机理和治疗研究进展[J].实用糖尿病杂志,2008,4(4):9-10.
[16] Lagathu C,Bastard JP,Auclair M,et al.Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte:prevention by rosiglitazone[J].Biochem Biophys Res Commun,2003,311(2):372-379.
[17] Barker G,Lim R,Georgiou HM,et al.Omentin-1 is decreased in maternal plasma,placenta and adipose tissue of women with pre-existing oObesity[J].PLoS One,2012,7(8):42943-42944.
[18] 马妍,吴雷.探讨Visfatin与糖脂代谢及2型糖尿病患者轻度认知障碍的相关性[J].中国医师杂志,2017,19(11):1676-1679.
[19] 姜文慧,吴秀萍.脂肪因子Apelin与2型糖尿病相关性的研究进展[J].国际生物医学工程杂志,2018,41(2):192-196.
[20] 罗景慧,杨迎暴.白黎芦醇对酒精性肝损伤大鼠血清中TNF-α、IL-6、ICAM-1水平的影响及机制中[J].中国药理与临床,2010,26(4):14-15.
[21] 黄敏贤,吴谦,潘竞锵,等.茵陈蒿汤对酒精性诱导脂肪肝大鼠的护肝、抗自由基损伤和降血脂作用[J].海峡药学,2015,27(2):21-24.
[2] Landgraf K,Friebe D,Ullrich T,et al.Chemerin as a mediator between obesity and vascular inflammation in children[J].J Clin Endocrinol Metab,2012,97(4):556-564.
[3] Greulich S,Chen WJ,Maxhera B,et al.Cardioprotective properties of omentin-1 in type 2 diabetes:evidence from clinical and in vitro studies[J].PLoS One,2013,8(3):59697-59698.
[4] Utzschneider KM,Kahn SE.Review:the role of insulin resistance in nonalcoholic fatty liver disease[J].J Clin Endocrinol Metab,2006,91(12):4753-4761.
[5] 周伟青,潘竞锵.茵陈蒿汤对慢性酒精性脂肪肝的疗效及机制研究[J].国际医药卫生导报,2010,16(18):2205-2207.
[6] 程斌,吕圭源,陈素红,等.银芍散对非酒精性单纯性脂肪肝模型大鼠防治作用的研究[J].中华中医药学刊,2016,34(5):1065-1069.
[7] 赵汝霞,郑琳颖,潘竞锵,等.白芍总苷对NAFLD模型大鼠肝脏保护作用的抗氧化机制[J].广东药学院学报,2012,28(4):430-434.
[8] 汪春燕.非酒精性脂肪肝的研究新进展[J].保健医学研究与实践,2011,8(1):8-11.
[9] Day CP,James OF.Steatohepatitis:a tale of two “hits”[J].Gastroenterology,1998,114(4):842-845.
[10] Rolo AP,Teodoro JS,Palmeira CM.Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis[J].Free Radic Biol Med,2012,52(1):59-69.
[11] 陈晓琳,唐成林,谢辉,等.电针对非酒精性脂肪性肝病大鼠肝TLR4、NF-κB表达的影响[J].南方医科大学学报,2014,34(11):1584-1588.
[12] 沈卫东,陈海姣,许庆华,等.HIF-1α信号在大鼠不同程度非酒精性脂肪性肝病中的表达[J].中华内分泌代谢杂志,2015,31(4):349-353.
[13] 苏如婷,韩晓骏.非酒精性脂肪肝病与胰岛素抵抗的相关性[J].实用医学杂志,2012,28(21):3551-3553.
[14] 陈容平,杨锐,陈宏.2型糖尿病合并非酒精性脂肪肝患者胰岛素抵抗的特点[J].广东医学,2011,32(8):1006-1007.
[15] 陈梅,宋爱华,程雪娟,等.非酒精性脂肪肝发病机理和治疗研究进展[J].实用糖尿病杂志,2008,4(4):9-10.
[16] Lagathu C,Bastard JP,Auclair M,et al.Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte:prevention by rosiglitazone[J].Biochem Biophys Res Commun,2003,311(2):372-379.
[17] Barker G,Lim R,Georgiou HM,et al.Omentin-1 is decreased in maternal plasma,placenta and adipose tissue of women with pre-existing oObesity[J].PLoS One,2012,7(8):42943-42944.
[18] 马妍,吴雷.探讨Visfatin与糖脂代谢及2型糖尿病患者轻度认知障碍的相关性[J].中国医师杂志,2017,19(11):1676-1679.
[19] 姜文慧,吴秀萍.脂肪因子Apelin与2型糖尿病相关性的研究进展[J].国际生物医学工程杂志,2018,41(2):192-196.
[20] 罗景慧,杨迎暴.白黎芦醇对酒精性肝损伤大鼠血清中TNF-α、IL-6、ICAM-1水平的影响及机制中[J].中国药理与临床,2010,26(4):14-15.
[21] 黄敏贤,吴谦,潘竞锵,等.茵陈蒿汤对酒精性诱导脂肪肝大鼠的护肝、抗自由基损伤和降血脂作用[J].海峡药学,2015,27(2):21-24.