高血压合并高脂血症大鼠模型的实验研究

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。

Establishment and characterization of a rat model of hypertension with hyperlipidemia

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 lipid analysis 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 AHP/ 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.