【摘要】 背景:脑脉通注射液是治疗缺血性脑血管病的中药复方制剂,具有拮抗钙超载,调节前列素与血栓素系统的失衡状态,阻断自由基介导的脂质过氧化反应而保护大脑。目的:观察脑脉通注射液对大鼠脑组织含水量和Ca2+含量、超氧化物歧化酶活性、脂质过氧化物、6-酮-前列素1α、血栓素水平的影响,并与复方丹参注射液做比较。设计:随机对照实验。单位:成都中医药大学实验中心。材料:实验于1997-10/1998-02成都中医药大学实验中心完成。选择健康雄性Wistar大鼠72只,随机分为6组,每组12只。①正常对照组:不进行模型制备,自由饮水,常规饲养。②模型组:腹腔注射生理盐水1.67mL/kg,2次/d。③复方丹参注射液1.67mL/kg组:腹腔注射复方丹参注射液1.67mL/kg,2次/d。④脑脉通注射液3.33,1.67,0.84mL/kg组:腹腔注射脑脉通注射液3.33,1.67,0.84mL/kg,2次/d。方法:各组大鼠用药48h后,于麻醉状态下快速断头处死,立即取出脑组织,从两半球中间切开分成两份,一份在低温下制备脑组织匀浆采用放射免疫分析法待测6-酮-前列素1α和血栓素B2水平评估前列素与血栓素系统的平衡状态、采用改进的邻苯三酚自氧化法和硫代巴比妥酸比色法检测超氧化物岐化酶活性和脂质过氧化物水平评估自由基介导的脂质过氧化情况。另一份立即在电子天平上称取干、湿重,计算脑组织含水量评估脑水肿情况。采用原子吸收分光光度法检测脑组织Ca2+含量评估钙超载情况。主要观察指标:①各组大鼠脑组织含水量和Ca2+含量。②各组大鼠脑组织超氧化物歧化酶活性、脂质过氧化物含量。③各组大鼠脑组织6-酮-前列素1α和血栓素B2含量。结果:72只大鼠均进入结果分析。①各组大鼠脑组织含水量和Ca2+含量:模型组明显高于正常组犤(82.27±1.32)%,(77.24±1.36)%;(267.47±15.69),(37.55±13.23)μg/g,P<0.01犦,4个治疗组的脑组织含水量均有不同程度的减轻,脑脉通注射液3.33mL/kg组效应最强犤(78.74±1.41)%犦,复方丹参注射液1.67mL/kg组最弱犤(81.45±1.52)%犦。复方丹参注射液各组Ca2+含量均有不同程度降低,存在剂量效应依赖性,而复方丹参注射液1.67mL/kg组Ca2+含量与模型组接近犤(253.66±12.85)μg/g,P>0.05犦。②各组大鼠脑组织超氧化物歧化酶活性、脂质过氧化物含量:模型组超氧化物歧化酶活性明显低于正常组犤(86.18±3.17),(131.86±4.67)μkat/g,P<0.01犦,经过治疗后脑脉通3个剂量组的超氧化物歧化酶活性均有提高,存在剂量效应依赖性(P<0.01),脑脉通注射液3.33mL/kg组效应最强犤(119.02±4.00)μkat/g犦,复方丹参注射液1.67mL/kg组超氧化物歧化酶活性与模型组接近(P>0.05)。模型组脂质过氧化物含量高于正常组犤(52.46±3.25),(32.29±2.23)μmol/L,P<0.01犦,各治疗组的脂质过氧化物含量均显著低于模型组,而脑脉通注射液3.33,1.67,0.84mL/kg组的疗效优于复方丹参注射液1.67mL/kg组犤(35.68±2.86),(41.54±2.47),(45.71±3.14),(47.84±2.71)μmol/L,P<0.01犦。③各组大鼠脑组织6-酮-前列素1α和血栓素B2含量:模型组脑组织6-酮-前列素1α含量明显低于正常组(P<0.01),4个治疗组均能提高6-酮-前列素1α含量,脑脉通注射液3.33,1.67,0.84mL/kg组的疗效优于复方丹参注射液1.67mL/kg组犤(43.84±2.98),(35.01±4.32),(29.97±3.81),(22.89±3.64)ng/g,P<0.01犦。模型组脑组织血栓素B2含量明显高于正常组(P<0.01),经治疗后4个治疗组与模型组比较均能显著降低脑组织血栓素B2含量,且存在剂量差异,而复方丹参注射液1.67mL/kg组的效果低于脑脉通注射液3.33,1.67,0.84mL/kg组犤(40.58±1.34),(32.85±1.43),(34.31±1.39),(37.27±1.52)ng/g,P<0.01犦。结论:脑脉通注射液可减轻脑水肿、拮抗钙离子、调节血栓素和前列腺素系统失衡、提高抗氧化酶活性和抗自由基损伤作用,从而起到保护脑组织结构和功能的治疗效应,且有一定的效量关系,脑脉通注射液的效果优于复方丹参注射液。更多还原

【Abstract】 BACKGROUND: Naomaitong injection is a Chinese herbal compound preparation for treatment of ischemic cerebral vascular disease, acting on resisting calcium overload, regulating the imbalance between thromboxane (TXA) and prostaglandin (PG) and blocking lipid peroxidation mediated by free radical so as to protect cerebrum. OBJECTIVE: To observe the effects of naomaitong injection on water and Ca2+ contents, activity of superoxide dismutase (SOD), levels of lipid peroxide (LPO), 6-keto-PG 1α and TXA, and compare it with danshen injection. DESIGN: Randomized control experiment was designed. SETTING: Experimental Center of Chengdu University of Traditional Chinese Medicine. MATERIALS: The experiment was performed in Experimental Center of Chengdu University of Traditional Chinese Medicine from October 1997 to February 1998, in which, 72 healthy male Wistar rats were employed, randomized into 6 groups, 12 rats in each. ① Normal control: The model was not prepared and the rats were free of drinking and bred routinely. ② Model group: Abdominal injection was done with physiological saline 1.67 mL/kg, twice/day. ③ Compound danshen injection 1.67 mL/kg group (danshen group): Abdominal injection was done with compound danshen injection 1.67 mL/kg, twice/day. ④ Naomaitong injection 3.33, 1.67, 0.84 mL/kg groups (naomaitong No.1, No.2 and No.3 groups): abdominal injection was done with naomaitong injection 3.33, 1.67, 0.84 mL/kg successively, twice/day. METHODS: Totally 48 hours after medication, under anesthetized state, the rats in every group were sacrificed to collect brain tissue. The two hemispheres were cut into two pieces from the middle. One of them was prepared into brain tissue homogenate at low temperature. Radioimmunologic analysis method was used to measure 6-keto-PG 1α and TXA B2 levels so as to evaluate the balance between PG and TXA systems. The modified pyorgallol autoxidation and thiobarbituric acid (TBA) colorimetric method were applied to determine SOD activity and LPO level respectively so as to evaluate lipid peroxidation mediated by free radical. The dry and wet weights of other piece were weighed immediately on electronic scale and the water content of brain tissue was calculated to evaluate brain edema. Atomic absorption spectrophotometry (AAS) was used to determine Ca2+content in brain tissue so as to evaluate calcium overload. MAIN OUTCOME MEASURES: ① Water and Ca2+ content in brain tissue of rats in every group. ② SOD activity and LPO level in brain tissue of rats in every group. ③ Contents of 6-keto-PG 1α and TXA B2 in brain tissue of rats in every group. RESULTS: Totally 72 rats all entered result analysis. ① Water and Ca2+content in brain tissue of rats in every group: That in model group was higher remarkably than normal group [(82.27±1.32)%, (77.24±1.36)%; (267.47±15.69), (37.55±13.23) μg/g, P < 0.01]. The water contents in 4 treatment groups were decreased of various degrees. The effect in No.1 group was the strongest [(78.74±1.41)%] and that in danshen group was the weakest[(81.45±1.52)%]. Ca2+ content in danshen group was decreased of various degrees, indicating dose-effect dependence, but, which was near to the result of model group [(253.66±12.85) μg/g, P > 0.05]. ② SOD activity and LPO level in brain tissue of rats in every group: SOD activity in model group was lower remarkably than normal group [(86.18±3.17), (131.86±4.67) μkat/g, P < 0.01]. After treated with naomaitong of 3 dosages, that was all improved, indicating dose-effect dependence (P < 0.01). The effect of No.1 group was the strongest [(119.02±4.00) μkat/g], SOD activity in danshen group was near to model group (P > 0.05). LPO level in model group was higher than normal group [(52.46±3.25), (32.29±2.23) μmol/L, P < 0.01]. LPO level of every treatment group was lower significantly than model group and the therapeutic effects of No.1, 2, 3 groups were superior to danshen group [(35.68±2.86), (41.54±2.47), (45.71±3.14), (47.84±2.71) μmol/L, P < 0.01]. ③ Contents of 6-keto-PG 1α and TXA B2 in brain tissue of rats in every group: Content of 6-keto-PG 1α in brain tissue of model group was lower remarkably than normal group (P < 0.01). That was improved in all of 4 treatment groups, in which, the therapeutic effects of No.1, 2, 3 groups were superior to danshen group [(43.84±2.98), (35.01±4.32), (29.97±3.81), (22.89±3.64) ng/g, P < 0.01]. TXA B2 content in brain tissue of model group was higher remarkably than normal group (P < 0.01). After treatment, the 4 treatment groups lowed significantly TXA B2 content in brain tissue compared with model group, indicating dose difference. That in danshen group was lower than No.1, 2, 3 groups [(40.58±1.34), (32.85±1.43), (34.31±1.39), (37.27±1.52) ng/g, P < 0.01]. CONCLUSION: Naomaitong injection alleviates brain edema, resists calcium ion, regulates imbalance between TXA and PG systems, improves activity of anti-oxidase and is against injury of free radical so as to protect the structure of brain tissue and achieve therapeutic effects, indicating a certain dose-effect relationship. The effect of naomaitong injection is superior to that of compound danshen injection.更多还原