高血压合并高脂血症大鼠模型的实验研究
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摘要
目的利用高脂饲料饲喂自发性高血压大鼠(SHR),构建高血压合并高脂血症大鼠模型,并对其心肾损伤进行评价,为高血压合并高脂血症治疗药物的评价提供药效学动物模型及相关方法参考。方法选取3周龄SHR随机分为空白对照组、模型组;同时选用同周龄正常血压的Wistar-Kyoto(WKY)大鼠作为模型对照组。空白对照组和模型对照组饲喂普通维持饲料,模型组饲喂高脂饲料,诱导SHR产生高血压合并高脂血症。造模期间定时测定各组大鼠的血压、体重,造模终点测定大鼠血压、血脂及体重后处死,收集心脏及肾脏组织并检测其纤维化损伤。结果 SHR高脂饲料饲喂23周后,血脂水平紊乱明显;心肾器官呈现明显的病理学改变:心肌细胞肥厚明显,肾组织小叶间动脉血管壁显著性重构,且心、肾组织严重纤维化。结论 SHR饲喂高脂饲料23周后可成功获得高血压合并高脂血症大鼠模型,其心脏及肾脏靶器官均呈现出明显的病理学改变,与人类高血压合并高脂血症临床表现较相似,有望广泛用作治疗高血压合并高脂血症的药物、或改善该类合并症心肾系统损伤的治疗药物的药效学评价模型。
Objective To develop an ideal hypertension combined hyperlipidemia( HP/HL) rat model by feeding spontaneously hypertensive rats( SHRs) with high fat diet,and to evaluate the pathological changes in target organs including heart and kidney. Methods Twenty 3-week old male SHRs were randomly divided into two groups: normal fat control group( SHR-NC) and high fat group( SHR-HF). Moreover,ten 3-week old male Wistar-Kyoto rats( WKY) were taken as the model control group( WKY-NC). The rats in SHR-HF group were fed with high-fat diet to induce HP/HL,while rats of WKY-NC and SHR-NC groups were fed with normal diet. The systolic blood pressure( SBP) and body weight were measured every week. At the end of the experiment,the rats were sacrificed to take serum samples for blood lipidanalysis including high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),total cholesterol( TC) and triglyceride( TG). Heart and kidney tissue samples were collected to examine the pathological changes using HE and Masson staining. Results Compared with the SHR-NC group,the SHRs fed with high-fat diet for 23 weeks presented significant increase of blood pressure and TC,TG,LDL-C,and decrease of HDL-C. The HP/HL rat model showed pathological changes in the HP/HL target organs,heart and kidney. Renal tissues were severely damaged and showed a large area of fibrosis. Besides,left ventricular hypertrophy and myocardial fibrosis were also observed. Conclusions A HP/HL rat model is successfully constructed by feeding SHRs with high-fat diet for 23 weeks. Most importantly,this model exhibits progressive renal and cardiac alterations,similar to those of patients with HP/HL. This HP/HL rat model may become widely used for evaluation of HP/HL therapeutic drugs.
Objective To develop an ideal hypertension combined hyperlipidemia( HP/HL) rat model by feeding spontaneously hypertensive rats( SHRs) with high fat diet,and to evaluate the pathological changes in target organs including heart and kidney. Methods Twenty 3-week old male SHRs were randomly divided into two groups: normal fat control group( SHR-NC) and high fat group( SHR-HF). Moreover,ten 3-week old male Wistar-Kyoto rats( WKY) were taken as the model control group( WKY-NC). The rats in SHR-HF group were fed with high-fat diet to induce HP/HL,while rats of WKY-NC and SHR-NC groups were fed with normal diet. The systolic blood pressure( SBP) and body weight were measured every week. At the end of the experiment,the rats were sacrificed to take serum samples for blood lipidanalysis including high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),total cholesterol( TC) and triglyceride( TG). Heart and kidney tissue samples were collected to examine the pathological changes using HE and Masson staining. Results Compared with the SHR-NC group,the SHRs fed with high-fat diet for 23 weeks presented significant increase of blood pressure and TC,TG,LDL-C,and decrease of HDL-C. The HP/HL rat model showed pathological changes in the HP/HL target organs,heart and kidney. Renal tissues were severely damaged and showed a large area of fibrosis. Besides,left ventricular hypertrophy and myocardial fibrosis were also observed. Conclusions A HP/HL rat model is successfully constructed by feeding SHRs with high-fat diet for 23 weeks. Most importantly,this model exhibits progressive renal and cardiac alterations,similar to those of patients with HP/HL. This HP/HL rat model may become widely used for evaluation of HP/HL therapeutic drugs.
引文
[1]Han TS,Lean ME.A clinical perspective of obesity,metabolic syndrome and cardiovascular disease[J].JRSM Cardiovasc Dis,2016,5:1-13.
[2]Bernhardi RV,Zanlungo S,Arrese M,et al.The metabolic syndrome:from an aggravating condition to a pathogenic risk factor for chronic diseases[J].Revista Medica De Chile,2010,138(8):1012-9.
[3]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2015》概要[J].中国循环杂志,2016,31(6):521-528.
[4]Bundy JD,He J.Hypertension and related cardiovascular disease burden in China[J].Annals Global Health,2016,82(2):227-233.
[5]殷玥琪,杨立刚,孙桂菊.高脂血症与高血压相关性及其代谢异常研究进展[J].中国老年学,2014,34(5):1414-1417.
[6]郑婧.自发性高血压大鼠心肌组织microRNA-97a与TGF-β1蛋白表达的改变及意义[J].中国比较医学杂志,2016,26(11):72-76.
[7]谢亚菲,蒋学华,王凌,等.Dunkin Hartley白化豚鼠和Hartley花色豚鼠高脂造模以及降脂药效学的比较[J].中国比较医学杂志,2015,25(9):56-61.
[8]刘晓敏,陈虹.“二肾一夹”复合高脂灌胃法建立高血压复合高脂血症大鼠模型[J].时珍国医国药,2008,19(2):306-307.
[9]程轶群,李晓辉.若干实验性高血压大鼠模型的介绍[J].中国比较医学杂志,2006,16(5):305-308..
[10]Jang SM,Yee ST,Choi J,et al.Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat die t[J].Int Immunopharmacol,2009,9(1):113-119.
[11]Knight SF,Quigley JE,Yuan J,et al.Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet[J].Hypertension,2008,51:352-359.
[12]夏晓莉,陈伯钧,刘泉颖,等.利用自发性高血压大鼠建立营养性高血压肥胖模型的研究进展[J].现代中西医结合杂志,2009,18(8):945-947.
[13]Knight SF,Yuan J,Roy S,et al.Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension[J].Am J Physiol Renal Physiol,2010,298(1):F86-94.
[14]Chung HW,Lim JH,Kim MY,et al.High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARα-Fox O3a-PGC-1αpathway[J].Nephrol Dial Transplant,2012,27:2213-2225.
[15]Chung S,Park CW,Shin SJ,et al.Tempol or candesartan prevents high-fat diet-induced hypertension and renal damage in spontaneously hypertensive rats[J].Nephrol Dial Transplant,2010,25:389-399.
[2]Bernhardi RV,Zanlungo S,Arrese M,et al.The metabolic syndrome:from an aggravating condition to a pathogenic risk factor for chronic diseases[J].Revista Medica De Chile,2010,138(8):1012-9.
[3]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2015》概要[J].中国循环杂志,2016,31(6):521-528.
[4]Bundy JD,He J.Hypertension and related cardiovascular disease burden in China[J].Annals Global Health,2016,82(2):227-233.
[5]殷玥琪,杨立刚,孙桂菊.高脂血症与高血压相关性及其代谢异常研究进展[J].中国老年学,2014,34(5):1414-1417.
[6]郑婧.自发性高血压大鼠心肌组织microRNA-97a与TGF-β1蛋白表达的改变及意义[J].中国比较医学杂志,2016,26(11):72-76.
[7]谢亚菲,蒋学华,王凌,等.Dunkin Hartley白化豚鼠和Hartley花色豚鼠高脂造模以及降脂药效学的比较[J].中国比较医学杂志,2015,25(9):56-61.
[8]刘晓敏,陈虹.“二肾一夹”复合高脂灌胃法建立高血压复合高脂血症大鼠模型[J].时珍国医国药,2008,19(2):306-307.
[9]程轶群,李晓辉.若干实验性高血压大鼠模型的介绍[J].中国比较医学杂志,2006,16(5):305-308..
[10]Jang SM,Yee ST,Choi J,et al.Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat die t[J].Int Immunopharmacol,2009,9(1):113-119.
[11]Knight SF,Quigley JE,Yuan J,et al.Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet[J].Hypertension,2008,51:352-359.
[12]夏晓莉,陈伯钧,刘泉颖,等.利用自发性高血压大鼠建立营养性高血压肥胖模型的研究进展[J].现代中西医结合杂志,2009,18(8):945-947.
[13]Knight SF,Yuan J,Roy S,et al.Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension[J].Am J Physiol Renal Physiol,2010,298(1):F86-94.
[14]Chung HW,Lim JH,Kim MY,et al.High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARα-Fox O3a-PGC-1αpathway[J].Nephrol Dial Transplant,2012,27:2213-2225.
[15]Chung S,Park CW,Shin SJ,et al.Tempol or candesartan prevents high-fat diet-induced hypertension and renal damage in spontaneously hypertensive rats[J].Nephrol Dial Transplant,2010,25:389-399.