基于中医辨证用药特点建立大鼠血热出血模型

Establishment of blood-heat and hemorrhage syndrome rat model based on Traditional Chinese Medicine characteristics

目的同时建立两种模拟中医临床血热出血证的大鼠模型,通过对比分析,对两种模型进行考察。方法模型Ⅰ(干姜组)以5%乙醇代替自由饮水,并灌胃干姜水煎剂,给药剂量15 g.kg-1;空白Ⅰ组自由饮水,并灌胃等体积蒸馏水,连续给药14 d。模型Ⅱ(干酵母组)采用皮下注射干酵母,注射剂量为2 g.kg-1,辅以体积分数5%乙醇代替自由饮水;空白Ⅱ组自由饮水,并皮下注射等体积生理盐水。观察大鼠一般体征(体重、饮食量、饮水量、尿量、粪便量、粪便含水量及肛温)的变化,血液流变仪测定全血和血浆黏度,全自动血细胞分析仪测定红细胞计数(RBC)、血红蛋白含量(HGB)及红细胞压积(HCT),凝血仪测定血浆凝血酶时间(TT)、纤维蛋白原(FIB)含量、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT),组织学检查舌、肺、胃的病理变化。结果造模14 d后,与空白Ⅰ组比较,干姜组大鼠体重相对减轻,饮食量、饮水量和尿量增加(P<0.05,P<0.01),粪便量及粪便含水量减少(P<0.01),肛温明显升高(P<0.01),全血高、中、低切黏度及血浆黏度明显增加(P<0.05,P<0.01),TT和APTT明显延长(P<0.01),PT缩短(P<0.01),FIB含量增加(P<0.01),RBC计数相对增加,HGB含量及HCT明显增加(P<0.05);与空白Ⅱ组比较,皮下注射干酵母4 h后,干酵母组大鼠肛温增加且稳定在较高水平(P<0.01),全血高、中、低切黏度及血浆黏度明显增加(P<0.05,P<0.01),TT和APTT明显延长(P<0.01),PT缩短(P<0.01),FIB含量增加(P<0.01),RBC、HGB及HCT明显增加(P<0.05,P<0.01)。光镜下观察,干姜和干酵母组大鼠舌、胃组织可见血管扩张,肺组织可见局灶性出血。结论大剂量干姜水煎剂灌胃或皮下注射干酵母混悬液均可引起大鼠血热出血,导致血液流变学指标异常、凝血功能障碍、组织血管扩张和出血现象,分析认为选择干姜为造模用药更符合中医临床内伤杂病、烧灼血络、血热妄行出血之特点。

Aim To establish and contrast two kinds of rat models of blood-heat and hemorrhage syndrome based on Traditional Chinese Medicine characteristics. Methods In model Ⅰ , rats were fed with the water decoction of Rhizoma Zingiberis （RZD） at the dose of 15 g · kg^-1 and 5% alcohol for 14 days continuously, and the rats in control group I were fed with water in the same volume. In model Ⅱ , rats were injected of dry yeast solutions subcutaneously at the dose of 2 g · kg^-1 and fed with 5% alcohol, and the physiological saline was given to the control group Ⅱ in the same volume. The amount of body weight, daily diet, volume of daily drinking and urine, pellet weight and its moisture capacity, rectal temperature were recorded. After 14 days, thrombin time （ TY）, fibrinogen content （ FIB ）, prothrombin time （ PT）, activated partial thromboplastin time （ APTT）,red blood cell （ RBC ） , hemoglobin （ HGB ） , hematocrit （ HCT ） and hemorheological parameters were examined, and the histological changes of tongue, lung, and stomach were observed by hematoxylin-eosin stain. Results After 14 days, the amount of body weight, rectal temperature and daily diet, the volume of daily drinking and urine of model I increased （ P 〈 0. 05, P 〈 0. 01 ）, while the pellet weight and its moisture capacity decreased （ P 〈 0. 01 ） with the comparison of control group Ⅰ Compared with control group Ⅱ , the rectal temperature of model Ⅱ was upgraded obviously（P 〈0. 01 ） four hours after the injection. Both model groups had significant difference compared with the control groups, the blood and plasma viscosity, RBC, HGB, HCT, TT, APTT and FIB were prolonged, （ P 〈 0. 05, P 〈 0. 01 ）and PTwas shortened （P 〈 0.01 ）. Vasodilatation in thetongue and stomach, and hemorrhage in the lung were also observed in the two model groups. Conclusion Giving a large dose of RZD orally or injecting dry yeast solutions subcutaneously can induce vasodilatation, hemorrhage, dysfunction of hemorrheology and coagulation system in SD rats, and modeling with RZD is more appropriate to describe the blood-heat and hemor-rhage syndrome based on traditional Chinese medicine characteristics.