不同活血化瘀方剂对重型颅脑损伤急性期大鼠的应用风险

Application Risk of Different Prescriptions for Activating Blood Circulation and Resolving Blood Stasis in Rats with Acute Severe Craniocerebral Injury

目的探讨不同活血化瘀方剂对重型颅脑损伤(s TBI)急性期大鼠的影响。方法 306只SD雄性大鼠随机分为正常组、模型组、脑蛋白水解物组、桃红四物汤、血府逐瘀汤组、通窍活血汤组、补阳还五汤组7组。除正常组外其余各组采用改良的Feeney’自由落体方法制备s TBI大鼠模型。造模成功后脑蛋白水解物组、桃红四物汤组、血府逐瘀汤组、通窍活血汤组、补阳还五汤组分别给予相应药物1. 11 mg/200 g、2. 04 g/200 g、3. 12 g/200 g、1. 92 g/200 g、5. 74 g/200 g灌胃,正常组和模型组给予生理盐水3 ml/200 g灌胃,各组每日均灌胃1次,连续7天。灌胃后随时统计大鼠死亡率,在第1、3、7天分别观察大鼠脑组织病理评分,检测血清微管相关蛋白Tau、胶质纤维酸性蛋白(GFAP)含量。结果实验期间正常组与脑蛋白水解物组大鼠无死亡,其余各组大鼠死亡主要集中在前4天,前4天与正常组比较,模型组、桃红四物汤组、血府逐瘀汤组大鼠死亡率都显著升高(P <0. 01);与模型组比较,桃红四物汤组、血府逐瘀汤组大鼠死亡率也明显升高(P <0. 01),而通窍活血汤组、补阳还五汤组差异无统计学意义(P> 0. 05)。与正常组同时间相比较,各给药组大鼠脑组织病理评分及血清Tau、GFAP水平在3个时间段均明显升高(P <0. 05)。与模型组同时间比较,第1天血府逐瘀汤组、通窍活血汤组和补阳还五汤组大鼠病理评分升高,桃红四物汤组、血府逐瘀汤组、补阳还五汤血清GFAP蛋白水平升高(P <0. 05);而在第3天除桃红四物汤组外,其余各给药组病理评分较模型组降低;脑蛋白水解物组、通窍活血汤组、补阳还五汤血清Tau、GFAP水平降低(P <0. 05);第7天各给药组病理评分及血清Tau、GFAP水平均降低(P <0. 05)。结论 s TBI急性期使用桃红四物汤及血府逐瘀汤会加重病情,增加死亡风险。用活血化瘀药来治疗s TBI急性期的最佳时间段可能在发生损伤第4天后,并且以通窍活血汤和补阳还五汤效果最好。

Objective To investigate the effect of different prescription for activating blood circulation and resolving blood stasis rats with severe traumatic brain injury( s TBI) in acute stages. Methods A total of 306 SD male rats were randomly divided into normal group,model group,brain protein hydrolysate group,Taohong Siwu Decoction( 桃红四物汤) group,Xuefu Zhuyu Decoction( 血府逐瘀汤) group,Tongqiao Huoxue Decoction( 通窍活血汤) group and Buyang Huanwu Decoction( 补阳还五汤) group. The s TBI rat model was prepared by the modified Feeney’ free fall method except the normal group. After successful modeling,the brain protein hydrolysate group,the Taohong Siwu Decoction group,the Xuefu Zhuyu Decoction group,the Tongqiao Huoxue Decoction group and the Buyang Huanwu Decoction group were intragastrically given the corresponding drugs 1. 11 mg/200 g,2. 04 g/200 g,3. 12 g/200 g,1. 92 g/200 g,5. 74 g/200 g respectively. The normal group and the model group were given normal saline 3 ml/200 g,and each group was intragastrically administered once a day for 7 days. The mortality of rats was counted at any time after intragastric administration. The pathological scores of brain tissue were observed on the 1 st,3 rd and 7 th day,and the contents of serum microtubule-associated protein Tau and glial fibrillary acidic protein( GFAP) were detected. Results During the experiment,there was no death in the normal group and the brain protein hydrolysate group. The deaths of the other groups were mainly during the first 4 days. Compared with the normal group,the death rate of the model group,the Taohong Siwu Decoction group and the Xuefu Zhuyu Decoction was significantly increased( P < 0. 01). Compared with the model group,the death rate of the Taohong Siwu Decoction group and the Xuefu Zhuyu Decoction group were also significantly increased( P < 0. 01). There was no significant difference between the Tongqiao Huoxue Decoction group and the Buyang Huanwu Decoction group( P > 0. 05). Compared with the normal group,the brain histopathological scores and serum Tau and GFAP levels in the rats in all treated groups were significantly increased at 3 time points( P < 0. 05). Compared with the model group at the same time point,the pathological scores of the rats in the Xuefu Zhuyu Decoction group,the Tongqiao Huoxue Decoction group and the Buyang Huanwu Decoction group increased on the first day,and the serum GFAP protein level of the Taohong Siwu Decoction group,the Xuefu Zhuyu Decoction group and the Buyang Huanwu Decoction group was increased( P < 0. 05). On the3 rd day,in all groups except the Taohong Siwu Decoction group,the pathological scores were lower than those of the model group;The serum Tau and GFAP levels of the brain protein hydrolysate group,the Tongqiao Huoxue Decoction group and the Buyang Huanwu Decoction group decreased( P < 0. 05). On the 7 th day,the pathological scores,serum Tau and GFAP levels of all treated groups decreased( P < 0. 05). Conclusion The use of Taohong Siwu Decoction and Xuefu Zhuyu Decoction in the acute phase of s TBI could aggravate the condition and increase the risk of death. The best time to treat the acute phase of s TBI with activating blood circulation and resolving blood stasis drugs may be after the 4 th day of injury,and the effect of Tongqiao Huoxue Decoction and Buyang Huanwu Decoction is the best.