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目的:由于“饮食不节、饮酒无度”与高黏血症密切相关,采用长期高盐、高脂、酒饮等复合因素诱导,观察对大鼠血液黏度、血压等的影响,并与高分子右旋糖酐造模比较,以期得到接近临床患者症候的慢性高黏血症动物模型,为中药药效评价奠定基础。方法:雄性SD大鼠分为正常对照组、高分子右旋糖酐(HMD)组、高盐高脂酒饮(HSFA)组。HMD组给予普通饲料喂养,自由饮水,第24天起尾静脉注射10%HMD,连续5 d;HSFA组给予高盐高脂饲料喂养,每天自由饮酒20 h,连续13周。造模5,8,11周测全血黏度(WBV)和血浆黏度(PV);5,7,10周测血压;11周测红细胞计数(RBC)、红细胞压积(HCT);13周测正常对照组和HSFA组血小板聚集率(PAgT)、血浆纤维蛋白原(Fb)及血清内皮素-1(ET-1)、一氧化氮(NO)、前列环素(PGI_2)、血栓素A2(TXA_2)含量,流式细胞术检测红细胞内钙离子(1ECa~(2+))含量。结果:造模后HMD组毛发光泽好、精神好、活动量多;HSFA组大鼠精神萎靡、毛色枯槁、活动量少。与正常对照组相比,造模5~11周HMD组和HSFA组大鼠高、低切全血黏度显著升高。HMD组血浆黏度仅第5周显著升高,HSFA组血浆黏度8,11周显著升高,并且第11周也显著高于HMD组。造模11周HSFA组RBC,HCT升高。造模后,HMD组血压无明显变化,HSFA组大鼠SBP第7~10周升高,其中第10周也显著高于HMD组。造模13周HSFA组PAgT,IECa~(2+),Fb,ET-1均明显升高,NO,PGI_2明显减少。结论:长期高盐高脂酒饮复合因素诱导可引起大鼠血液黏度异常。第5周起全血黏度显著升高,第8周起血浆黏度显著升高。该法升高血液黏度的机制可能是:RBC,HCT,IECa~(2+)增加;PAgT增加;Fb含量增加;TXA_2/PGI_2,ET-1/NO失衡。虽然该法造模时间比高分子右旋糖酐法长,但采用复合因素造模,模型更稳定,可缓慢、持续引起全血及血浆黏度异常升高,不同于高分子右旋糖酐法一过性升高血浆黏度,同时可引起SBP异常升高。模型大鼠体征更接近高黏血症中医证候,造模机制更接近患者发病机制,对中药药效学研究更有应用价值。
OBJECTIVE: To observe the effect of long-term high salt, high fat and alcohol drink on the blood viscosity and blood pressure of rats and its correlation with hyperviscosity Macromolecular dextran modeling in order to get close to clinical symptoms of patients with chronic hyperviscosity animal model for the evaluation of Chinese medicine to lay the foundation for the evaluation. Methods: Male SD rats were divided into normal control group, high molecular dextran (HMD) group and high salt and high fat drinks (HSFA) group. The rats in HMD group were fed with normal diet and were free to drink water. The tail vein was injected with 10% HMD on the 24th day for 5 consecutive days. The HSFA group was given high salt and high fat diet for 20 hours a day for 13 weeks. Whole blood viscosity (WBV) and plasma viscosity (PV) were measured 5, 8, and 11 weeks after operation. Blood pressure was measured at 5, 7 and 10 weeks; RBC and HCT were measured at 11 weeks; PAgT, Fb, ET-1, NO, PGI_2 and TXA2 in normal control group and HSFA group were higher than those in control group TXA_2) content was detected by flow cytometry intracellular calcium (1ECa ~ (2+)) content. Results: HMD group had good hair luster, good spirits and high activity after modeling. The rats in HSFA group were apathetic and withered, with less activity. Compared with the normal control group, the viscosity of whole blood of high and low cut of HMD group and HSFA group were significantly increased from 5 to 11 weeks after modeling. The plasma viscosity of HMD group increased significantly only at 5 weeks, and the plasma viscosity of HSFA group increased significantly at 8 and 11 weeks and also significantly higher than HMD group at 11 weeks. After 11 weeks of HSFA, RBC and HCT increased. After modeling, there was no significant change in the blood pressure of HMD group, SBP of HSFA group increased from the 7th week to the 10th week, and the 10th week was also significantly higher than the HMD group. The levels of PAgT, IECa ~ (2 +), Fb and ET-1 in HSFA group at 13th week after modeling were significantly increased, NO and PGI_2 were significantly decreased. Conclusion: Long-term high-salt, high-fat, alcohol-induced drinking complex factors can cause abnormal blood viscosity in rats. From the fifth week, the whole blood viscosity increased significantly, and the plasma viscosity increased significantly from the eighth week. The mechanism of this method to increase blood viscosity may be: RBC, HCT, IECa ~ (2+) increased; PAgT increased; Fb increased; TXA_2 / PGI_2, ET-1 / NO imbalance. Although the method of modeling time longer than the molecular dextran method, but the use of composite factor modeling, the model is more stable and can be slow, continued to cause abnormal increase in whole blood and plasma viscosity, unlike the polymer dextran transiently elevated plasma Viscosity, at the same time can cause abnormal SBP rise. The signs of model rats are more close to TCM syndromes of hyperviscosity syndrome, and the modeling mechanism is closer to the pathogenesis of patients, which is more valuable for the study of pharmacodynamics of Chinese medicine.