血府逐瘀汤对不可预见性刺激致血瘀的作用及机制

Effect and Mechanism of Xuefu Zhuyu Tang on Unpredictable Stimulus-induced Blood Stasis

目的:探讨血府逐瘀汤对不可预见性刺激致血瘀的作用及机制。方法:将SPF级大鼠随机分成正常组,模型组,血府逐瘀汤高、低剂量组,采用多因素联合刺激法复制血瘀证模型5周,同时ig给予生药量为105.3,35.1 g·kg^(-1)血府逐瘀汤,采用多因素刺激法建立气滞血瘀证动物模型;采用"飞点"法动态模拟微循环血流速度;采用激光多普勒技术检测组织血流量;采用凝固法检测凝血;采用分光光度法检测血浆中一氧化氮(NO),一氧化氮合成酶(NOS)活性;采用逆转录-聚合酶链反应方法检测NOS基因的表达。结果:与正常组比较,模型组大鼠体重增加速度缓慢;与模型组比较,血府逐瘀汤能改善大鼠体重增长缓慢的状态(P<0.05)。与正常组比较,模型组能明显降低微动脉,微静脉血流速度,收缩微动脉、微静脉血管管径(P<0.05);与模型组比较,血府逐瘀汤能显著增加大鼠肠系膜微动脉,微静脉血流速度,扩张微动脉、微静脉血管管径(P<0.05),显著增加大鼠皮肤、肝、肠血流量(P<0.05),显著降低大鼠纤维蛋白原含量(P<0.05);显著增加大鼠肝,肠,胃,卵巢,子宫血流量(P<0.05)。与正常组比较,模型组大鼠血浆中NO含量均显著降低(P<0.01),大鼠肝脏总NOS(TNOS)酶活性,结构型NOS(c NOS)酶活性与内皮型NOS(e NOS)基因表达水平显著降低(P<0.01);与模型组比较,血府逐瘀汤均能显著升高大鼠血浆中NO含量(P<0.01),大鼠肝脏TNOS,c NOS酶活性与e NOS基因表达水平显著高于模型组(P<0.05)。结论:血府逐瘀汤可以改善不可预见性刺激导致的血瘀症状,其逐瘀作用与气体信号分子NO存在相关性。

Objective： To discuss the effect and mechanism of Xuefu Zhuyu Tang on the unpredictable stimulus-induced blood stasis. Method： SPF grade rats were randomly divided into normal group, model group, Xuefu Zhuyu Tang high dose group and low dose group. Multi-factors combined stimulation method was used for 5 weeks to create blood stasis syndrome models, and at the same time, 105.3, 35.1 g -kg-l Xuefu Zhuyu Tang was given by gavage. Multi-factors stimulation method was used to establish the animal models of ＇ qi stagnation and blood stasis syndrome＇, ＇flying spot＇ method was used to dynamically simulate blood flow velocity in microcirculation, laser doppler technology was used to detect blood flow volume of the tissues, coagulation method was used to detect the blood coagulation, spectrophotometric method was used to determine plasma nitric oxide （NO）, and nitric oxide synthase （NOS） activity, reverse transcription-polymerase chain reaction RT-PCR method was used to detect the expression of NOS mRNA. Result： Compared with the normal group, rate of weight gain in rats of the model group was lower than that in the normal group. Compared with the model group, Xuefu Zhuyu Tang could improve the condition of slow growth rats for body weight （P 〈 0.05 ）. Co,npared with the normal group, the arteriole and venule blood flow rates were significantly decreased in the model group, and the arteriole and venule vessel diameters were significantly contracted （P 〈 0.05）. Compared with the model group, the rats in treatment groups could significantly increase the mesenteric arteriole and venule blood flow rates, and significantly dilate the arteriole and venule vessel diameters （P 〈 0.05） , significantly increase the blood flow volume of skin, liver, and intestine （P 〈 0.05） , significantly reduce fibrinogen levels （P 〈 0.05） , and significantly increase the blood flow volume of liver, intestine, stomach, ovarian and uterine （P 〈 0.05）. Compared with the normal group, NO content in plasma of rats in model group was significantly lower （P 〈 0.01 ）, liver total NOS （TNOS） activity, constitutive NOS （cNOS） activity and endothelial NOS （eNOS） gene expression levels were significantly lower （P 〈0.01）. Compared with the model group, NO levels in plasma （P 〈 0.01 ）, liver TNOS activity, cNOS activity and eNOS gene expression levels were significantly higher in the treatment groups （P 〈 0.05 ）. Conclusion： Xuefu Zhuyu Tang can improve the symptoms of blood stasis caused by unpredictable stimulus, and its action mechanism may be associated with the gas signal molecule NO.