摘要
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 composite factors, like long-term high-salt ＆ fat diet and alcohol abuse on blood vis- cosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medi- cines. Method： Male SD rats were randomly divided into the normal group, the high molecular dextran （HMD） group and the high salt ＆ fat and alcohol （HSFA） group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h · d-1 for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5th, 7th, and10th week. Red cell count （RBC） and hematocrit （HCT） were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI2, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa2~ content was measured with flow cytometry. Result： After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity （WBV） than the normal control group. The plasma viscosity （PV） of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8th and 11th week, particularly in the 11th week. In the 11th week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no sig- nificant changes, but the blood pressure of HSFA rats significantly increased during 7th and 10th weeks, particularly in the 10th week. In the 13th week, PAgT, IECa2＋ , Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2. Conclusion： Long- term high salt ＆ fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BY may be： ①increases in RBC, HCT, and IECa2＋ , ② PAgT in- crease, ③ Fb content increase, or ④ TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2015年第8期1560-1564,共5页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81374003
81274123)
国家"重大新药创制"科技重大专项(2011ZX09102-011-07)
浙江省卫生高层次创新人才培养工程项目(浙卫发[2010]190号)
浙江省重点实验室项目(2012E10002)
关键词
高黏血症
高盐高脂
血液流变学
高分子右旋糖酐
饮食不节
大鼠
中药
模型
hyperviscosity
high salt and high fat diet
hemorheology
high molecular dextran
improper diet
rat
traditional Chinese medicine
