蜂毒溶血肽改善非酒精性脂肪肝大鼠肝组织脂肪沉积作用及其机制研究*

doi:10.3969/j.issn.1672-5069.2019.04.006

摘要/Abstract

摘要： 目的探讨蜂毒溶血肽对非酒精性脂肪性肝病（NAFLD）大鼠肝脂肪变性的保护作用及其机制。方法随机将40只SD大鼠分成对照组、模型组、小剂量蜂毒溶血肽处理组和大剂量蜂毒溶血肽处理组。采用高脂饲料喂养建立NAFLD模型,再分别给予蜂毒溶血肽10 μg·kg^-1·d^-1和100μg·kg^-1·d^-1或生理盐水皮下注射,连续12 w。采用Western blot法检测核转录因子E2相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）表达。结果大剂量蜂毒溶血肽处理组大鼠体质量和肝质量分别为（380.2±20.8） g和（10.4±1.3） g,显著低于模型组【分别为（435.2±22.1） g和（14.3±1.4） g,P<0.05】,血清AST和ALT水平分别为（88.0±10.4） U/L和（49.3±6.2） U/L,显著低于模型组【分别为（159.7±18.9） U/L和（77.7±6.8）U/L,P<0.05】,血糖、TC、TG和LDL-C水平分别为（8.7±1.8） mmol/L、（1.6±0.2） mmol/L、（0.8±0.1）mmol/L和（0.3±0.1） mmol/L,显著低于模型组【分别为（18.3±2.4）mmol/L、（2.8±0.3） mmol/L、（1.5±0.2） mmol/L和（0.5±0.1）mmol/L,P<0.05】,血清超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽（GSH）水平分别为（82.1±6.6） U/L、（6.3±0.8） nmol/mL和（8.7±0.9） mmol/L,与模型组的（30.4±5.3）U/L、（13.1±1.6） nmol/mL和（2.3±0.5） mmol/L比,差异显著（P<0.05）,肝组织Nrf2和HO-1表达分别为（1.4±0.2）和（1.2±0.1）,显著高于模型组【分别为（0.3±0.1）和（0.3±0.1）,P<0.05】。结论蜂毒溶血肽可以调节NAFLD大鼠血糖和血脂代谢,减轻肝脂肪变程度,改善肝功能,其机制可能与调控Nrf2和HO-1表达,缓解氧化应激损伤有关。

关键词: 肝脂肪变, 蜂毒溶血肽, 核转录因子E2相关因子 2, 血红素加氧酶-1, 大鼠

Abstract: Objective To explore the protective effect of bee venom hemolysin on rats with nonalcoholic fatty liver disease （NAFLD）.Methods Forty male SD rats were randomly divided into control,model,low-dose and high dose of bee venom hemolysin-intervened groups. Rats were fed with high fat to establish the NAFLD models,and the bee venom hemolysin peptide at doses of 10 μg·kg^-1 and 100 μg·kg^-1 or saline were subcutaneously injected daily for 12 weeks. Hepatic expression of nuclear factor-erythroid 2 p45-related factor 2 （Nrf2） and heme oxygenase-1（HO-1） were detected by Western bloting.Results The body weight and liver mass of rats in high dose of bee venom hemolysin-intervened group were（380.2±20.8） g and（10.4±1.3） g,significantly lower than（435.2±22.1） g and （14.3±1.4） g in the model （P<0.05）,serum AST and ALT levels were （88.0±10.4） U/L and （49.3±6.2） U/L,much lower than （159.7±18.9） U/L and （77.7±6.8） U/L in the model （P<0.05）,blood glucose,TC,TG,and LDL-C levels were（8.7±1.8） mmol/L,（1.6±0.2） mmol/L,（0.8±0.1） mmol/L and （0.3±0.1）mmol/L,significantly lower than （18.3±2.4） mmol/L,（2.8±0.3） mmol/L,（1.5±0.2） mmol/L and （0.5±0.1）mmol/L,respectively in the model （P<0.05）,serum superoxide dismutase（SOD）,malondialdehyde（MDA） and glutathione（GSH） levels were （82.1±6.6）U/L,（6.3±0.8）nmol/mL and （8.7±0.9） mmol/L,significantly different as compared to （30.4±5.3）U/L,（13.1±1.6）nmol/mL and（2.3±0.5）mmol/L in the model（P<0.05）,hepatic expression of Nrf2 and HO-1 were （1.4±0.2） and （1.2±0.1）,significantly intensified as compared to（0.3±0.1） and （0.3±0.1） in the model （P<0.05）. Conclusion Bee venom hemolytic peptide might alleviate hepatic steatosis in rats with non-alcoholic fatty liver disease and improve liver function,and the mechanism might be related to the regulation of Nrf2 and HO-1 expression and relieve oxidative stress injury.

Key words: Liver steatosis, Bee venom hemolytic peptide, Nuclear factor-erythroid 2 p45-related factor 2, Heme oxygenase-1, Rats

王艳, 苏峰, 李园园, 李舒. 蜂毒溶血肽改善非酒精性脂肪肝大鼠肝组织脂肪沉积作用及其机制研究^*[J]. 实用肝脏病杂志, 2019, 22(4): 474-477.

Wang Yan, Su Feng, Li Yuanyuan, et al. Protective effect of bee venom hemolysin on rats with nonalcoholic fatty liver disease[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(4): 474-477.

参考文献

[1] 管军,徐烨. 青少年NAFLD相关危险因素分析. 实用肝脏病杂志,2017,20(3):347-349.
[2] Derra A,Bator M,Menzyk T,et al.Underrated enemy-from non-alcoholic fatty liver disease to cancers of the gastrointestinal tract. Clin Exp Hepatol,2018,4(2):55-71.
[3] Dumitrascu DL,Neuman MG.Non-alcoholic fatty liver disease:an update on diagnosis. Clujul Med,2018,91(2):147-150.
[4] Hanafi MY,ELM Z,SEM E,et al.The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD-induced non-alcoholic fatty liver in rats. Exp Ther Med,2018,15(6):5091-5099.
[5] Wang S,Xu M,Li X,et al.Exosomes released by hepatocarcinoma cells endow adipocytes with tumor-promoting properties. J Hematol Oncol,2018,11(1):82.
[6] Umehara T.Nonalcoholic fatty liver disease with elevated alanine aminotransferase levels is negatively associated with bone mineral density:Cross-sectional study in U.S. adults. PLoS One,2018,13(6):e0197900.
[7] CBM S,de Carli LA,Fantinelli M,et al. Impact of diabetes mellitus and insulin on nonalcoholic fatty liver disease in the morbidly obese. Ann Hepatol,2018,17(4):585-591.
[8] Juárez-Hernández E,C CN,C BD,et al. Association between serum hemoglobin levels and non alcoholic fatty liver disease in a Mexican population. Ann Hepatol,2018,17(4):577-584.
[9] Osaka T,Hashimoto Y,Hamaguchi M,et al.Nonalcoholic fatty liver disease remission in men through regular exercise. J Clin Biochem Nutr,2018,62(3):242-246.
[10] Dongiovanni P,Meroni M,Mancina RM,et al.Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nonalcoholic fatty liver disease. Hepatol Commun,2018,2(6):666-675.
[11] 邢英,李雅丽,郑嵘炅,等. 利拉鲁肽对NAFLD大鼠胰岛素抵抗的改善作用. 实用肝脏病杂志,2017,20(6):668-671.
[12] 李笠,梁学亚. 水飞蓟宾葡甲胺联合多烯磷脂酰胆碱治疗酒精性脂肪肝患者初步临床研究. 实用肝脏病杂志,2017,20(4):412-415.
[13] Sookoian S,Flichman D,Garaycoechea ME,et al.Metastasis-associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune-mediated liver damage. Hepatol Commun, 2018,2(6):654-665.
[14] Britton L,Bridle K,Reiling J,et al.Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease. Hepatol Commun,2018,2(6):644-653.
[15] Cai S,Ou Z,Liu D,et al.Risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patient with component of metabolic syndrome. United European Gastroenterol J,2018,6(4):558-566.
[16] 赵泽华,刘晓琳,范建高. 重视非酒精性脂肪性肝病自然史的研究. 中华肝脏病杂志,2017,25(2):81-84.
[17] Yan H,Gao YQ,Zhang Y,et al.Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease. J Biosci,2018,43(2):287-294.
[18] Fujii Y,Nanashima A,Hiyoshi M,et al.Risk factors for development of nonalcoholic fatty liver disease after pancreatoduodenectomy. Ann Gastroenterol Surg,2017,1(3):226-231.
[19] Chartampilas E.Imaging of nonalcoholic fatty liver disease and its clinical utility. Hormones (Athens),2018,17(1):69-81.
[20] Pfirrmann D,Haller N,Huber Y,et al.Applicability of a web-based individualized exercise intervention in patients with liver disease,cystic fibrosis,esophageal cancer,and psychiatric disorders:process evaluation of 4 ongoing clinical trials. JMIR Res Protoc,2018,7(5):e106.

蜂毒溶血肽改善非酒精性脂肪肝大鼠肝组织脂肪沉积作用及其机制研究^*

Protective effect of bee venom hemolysin on rats with nonalcoholic fatty liver disease

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	徐飞, 李伟荣. 黄芪甲苷对CCL₄所致肝损伤大鼠的保护作用^*[J]. 实用肝脏病杂志, 2019, 22(6): 808-811.
[2]	高磊, 曹蕾, 王瑞芳, 冯丹丹, 薛娟. 人脐带间充质干细胞移植对酒精性肝损伤大鼠的保护作用^*[J]. 实用肝脏病杂志, 2019, 22(6): 812-815.
[3]	林秋香, 王雪雯, 黄祖雄, 潘晨. 灯盏花素对肝脏缺血再灌注损伤大鼠肝脏和肠黏膜屏障功能的保护作用*[J]. 实用肝脏病杂志, 2019, 22(5): 636-639.
[4]	石小龙, 杜睿, 秦革萍, 薛华燕, 张宏鑫. 七氟醚对脓毒症大鼠肝损伤的保护作用及其作用机制研究*[J]. 实用肝脏病杂志, 2019, 22(5): 640-643.
[5]	周丽云, 李校天, 李丽, 杨俊超. 1,25（OH）₂D₃通过调节miR-146a水平抑制大鼠肝纤维化的体内和体外观察[J]. 实用肝脏病杂志, 2019, 22(3): 333-336.
[6]	郭丽平, 张成宏, 宁宝烁, 许敏, 徐贝贝, 王雪, 李异玲. 一种新生大鼠肝细胞分离改良方法的建立^*[J]. 实用肝脏病杂志, 2019, 22(1): 17-20.
[7]	玉苏甫·吐尔逊, 赵燕霞. 小剂量二乙基亚硝胺诱导大鼠肝纤维化模型的建立[J]. 实用肝脏病杂志, 2019, 22(1): 33-36.
[8]	刘恩强, 陈果, 廖修用, 许美凤, 魏贵玉, 罗小平. 虾青素对肝纤维化大鼠的保护作用及机制研究^*[J]. 实用肝脏病杂志, 2018, 21(6): 842-846.
[9]	隋菱, 杜纪坤, 郑静彬, 蔡国弟, 李莉. 姜黄素对CCl₄所致急性肝损伤大鼠的保护作用及其机制研究^*[J]. 实用肝脏病杂志, 2018, 21(5): 709-712.
[10]	高翔, 尚双艳. 复方鳖甲软肝片对二乙基亚硝胺所致原发性肝癌大鼠肝组织PCNA和α-SMA表达的影响^*[J]. 实用肝脏病杂志, 2018, 21(4): 553-556.
[11]	陈辉, 任万雷, 杨爱婷. 肝脏前体细胞移植对CCl4诱导的肝纤维化自发逆转大鼠肝组织学的影响*[J]. 实用肝脏病杂志, 2018, 21(3): 376-379.
[12]	刘晓琳, 信丰智, 杨蕊旭, 赵泽华, 周达, 潘勤, 范建高. 茵栀黄口服液对非酒精性脂肪性肝炎大鼠肝脂肪变的保护作用研究*[J]. 实用肝脏病杂志, 2018, 21(3): 380-383.
[13]	胡建鹏, 宋正己, 李玉莲, 寻琳婷, 赵雪茹, 张镕. 硫代乙酰胺诱导的急性肝损伤大鼠肝组织Norrin/Frizzled-4表达的变化*[J]. 实用肝脏病杂志, 2018, 21(2): 187-190.
[14]	尚双艳, 高翔. 香附多糖对牛血清白蛋白诱导的肝纤维化大鼠血清MMP-2、TIMP-2和TGF-β1水平的影响[J]. 实用肝脏病杂志, 2018, 21(1): 42-45.
[15]	邢英, 李雅丽, 郑嵘炅, 玛依拉·卡哈尔, 木胡牙提·乌拉斯汉. 利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用*[J]. 实用肝脏病杂志, 2017, 20(6): 668-671.