肝郁—脾虚—肝郁脾虚不同证候模型大鼠血液流变学变化及疏肝健脾方的作用

Hemorheological Changes in Rats with Syndromes of Liver Stagnation, Spleen Deficiency, Liver Stagnation with Spleen Deficiency, and Influence of Liver-soothing and Spleen-invigorating Recipe

【目的】比较肝郁证、脾虚证及肝郁脾虚证模型大鼠血液流变学状态和柴疏四君子汤对其影响。【方法】选用Wistar大鼠随机分为正常对照组、肝郁模型组、肝郁干预组、脾虚模型组、脾虚干预组、肝郁脾虚模型组和肝郁脾虚干预组共7组,每组8只。分别采用慢性束缚、过度疲劳+饮食失节法、慢性束缚+过度疲劳+饮食失节法复制肝郁、脾虚和肝郁脾虚证大鼠模型;于造模第15天,各模型干预组大鼠分别给予柴疏四君子汤3.57g·kg-1·d-1灌胃,各模型组和正常组给予等量蒸馏水,连续14d,测定各组大鼠血液流变学指标。【结果】与正常组比较,肝郁模型组、脾虚模型组和肝郁脾虚模型组大鼠在10/s、60/s、150/s切变率下全血黏度(ηb)和还原黏度(WBRV)均显著升高(P<0.05或P<0.01),脾虚模型组和肝郁脾虚模型组大鼠红细胞压积(Ht)均显著升高(P<0.05或P<0.01),血浆黏度(ηp)、红细胞电泳指数均显著降低(P<0.05),肝郁模型组大鼠ηp显著升高(P<0.05);与肝郁模型组比较,脾虚模型组和肝郁脾虚模型组大鼠ηp、红细胞电泳指数均显著降低(P<0.05或P<0.01),肝郁脾虚模型组Ht显著升高(P<0.05);与脾虚模型组比较,肝郁脾虚模型组大鼠低切变率下的ηb显著性升高(P<0.05)。与相应模型组比较,肝郁干预组大鼠在10/s切变率下ηb、Ht、红细胞聚集指数(RE)均显著升高(P<0.05),红细胞变形指数(TK)显著降低(P<0.05);脾虚干预组大鼠ηp显著升高(P<0.05);肝郁脾虚干预组大鼠ηp及电泳指数均显著性升高(P<0.05),低、高切率ηb及Ht均显著降低(P<0.05)。【结论】肝郁、脾虚、肝郁脾虚3证模型大鼠均存在不同程度的血液高黏状态,但肝郁证模型血液高黏状态主要与血液中的血小板及其他大分子成分的变化有关,脾虚证和肝郁脾虚证血液黏度升高与红细胞自身流变性质变化及血小板有关。柴疏四君子汤对肝郁脾虚证的血液流变学异常具有一定的改善作用,对脾虚证作用不明显,对肝郁证不仅无作用,甚或加重其异常。疏肝健脾方与肝郁脾虚证具有较高的关联性。

Objective To compare the hemorheological changes in rats with liver stagnation （LS） syndrome, spleen deficiency （SD） syndrome and liver stagnation with spleen deficiency （LSSD） syndrome, observe the influence of Chaishu Sijunzi Decoction （CSD） , a Chinese herbal medicine with the actions of soothing liver and invigorating spleen, on the hemorheology of model rats. Methods Wistar rats were randomly divided into normal group, LS group, LS intervention group, SD group, SD intervention group, LSSD group, and LSSD intervention group , 8 rats in each group. The chronic restraint stress method, excess fatigue ＋ improper diet method, chronic restraint stress ＋ excess fatigue ＋ improper diet method were used to establish LS model, SD model and LSSD model, respectively. On the 15th day of modeling, the rats in the three medication groups were given gastric use of CSD 3.57 g-kg-1·d-1, and the rats in the three model groups and normal group were given oral use of equal volume of distilled water, lasting for 14 days. Before and after treatment, the hemorheological parameters were detected. Results Compared with the normal group, whole blood viscosity and whole blood reduced viscosity （WBRV） at shear rate of 10, 60 and 150/s were all significantly increased in LS, SD and LSSD groups （P〈0.05 or P〈0.01）, hematocrit was enhanced （P〈0.05 or P〈0.01）, and plasma viscosity and erythrocyte eleetrophoresis index were declined （P〈0.05） in SD and LSSD groups, plasma viscosity was increased （P〈0.05） in LS group. Compared with LS group, plasma viscosity and erythrocyte electrophoresis index in SD and LSSD groups were markedly declined （P〈0.05 or P〈0.01）, and hematocrit in LSSD group was increased （P〈0.05）. Compared with SD group, low-shear whole blood viscosity in LSSD group was increased （P〈0.05）. Compared with the corresponding model groups, whole blood viscosity, hematocrit and erythrocyte aggregation index at low shear rate were increased （P〈0.05） and erythrocyte deformation index was declined （P〈0.05） in LS intervention group, plasma viscosity was markedly increased （P〈0.01） in SD intervention group, and plasma viscosity and erythroeyte electrophoresis index were increased （P〈0.05） while low- and high-shear hematorit and whole blood viscosity were declined （P〈0.05） in LSSD intervention group. Conclusion Various degrees of increased blood viscosity occur in LS, SD and LSSD model rats. High blood viscosity in LS model rats is related with the changes of platelets and other blood macromoleeule components, and the increase of blood viscosity has relevance with erythrocyte theological property and platelets. Chaishu Sijunzi Decoction has certain effect on hemorheological disorder in LSSD model rats, has no obvious effect on that in SD model rats, but has effect on promoting the aggravation of hemorheological disorder in LS model rats. The above results provide the experimental evidence for LSSD syndrome being the indications of Chaishu Sijunzi Decoction.