赤芍总苷对大鼠局灶性脑缺血再灌注损伤的保护效果

Protective effects of total paeony glycoside against focal cerebral ischemia/reperfusion injury in rats

目的:观察赤芍总苷对大鼠局灶性脑缺血再灌注损伤的作用并分析可能的作用机制。方法:实验于2005-11/2006-01在安徽医科大学基础医学院生理教研室与药理学教研室完成。健康Wistar大鼠100只,随机数字表法分成5组:假手术组,模型组,赤芍总苷3mg/kg组,赤芍总苷6mg/kg组,阳性药物组(灌胃灯盏花素),每组20只。赤芍总苷3mg/kg组、赤芍总苷6mg/kg组和阳性药物组分别灌胃相应的药物,给药容积为5mL/kg体质量,1次/d,连续6d。假手术组与模型组分别灌胃等量的生理盐水。应用线栓法制备大鼠局灶性脑缺血再灌注模型,观察缺血2h再灌注24h后赤芍总苷对大鼠脑组织梗死面积(梗死百分比=梗死灶质量/右侧大脑半球质量×100%)、丙二醛含量及乳酸脱氢酶活性、Na+-K+-AT-Pase与Ca2+-ATPase活性的影响。结果:实验大鼠100只均进入结果分析。①实验大鼠脑组织梗死面积百分比:赤芍总苷3mg/kg组、赤芍总苷6mg/kg组、阳性药物组与模型组相比均减少[模型组(27.4±3.3)%,赤芍总苷3mg/kg组(23.3±3.6)%,赤芍总苷6mg/kg组(18.2±5.3)%,阳性药物组(19.3±4.1)%,P<0.05～0.01]。②实验大鼠脑组织中丙二醛和乳酸脱氢酶含量:模型组与假手术组相比丙二醛含量升高,乳酸脱氢酶活性降低,赤芍总苷3mg/kg组、赤芍总苷6mg/kg组、阳性药物组与模型组相比,可降低脑组织中的丙二醛含量,增高脑组织中乳酸脱氢酶活性[丙二醛含量:假手术组(2.11±0.32)μmol/g,模型组(7.43±1.24)μmol/g,赤芍总苷3mg/kg组(3.14±0.77)μmol/g,赤芍总苷6mg/kg组(2.54±1.08)μmol/g,阳性药物组(2.86±0.83)μmol/g;乳酸脱氢酶活性:假手术组(55.84±3.50)μkat/g,模型组(20.50±2.17)μkat/g,赤芍总苷3mg/kg组(28.01±5.83)μkat/g,赤芍总苷6mg/kg组(44.34±4.50)μkat/g,阳性药物组(34.01±5.17)μkat/g,P<0.05～0.01]。③实验大鼠脑组织中Na+-K+-ATPase与Ca2+-ATPase活性:模型组与假手术组相比均降低,赤芍总苷3mg/kg组、赤芍总苷6mg/kg组、阳性药物组与模型组相比均升高[Na+-K+-ATPase活性:假手术组(21.54±4.98)mkat/g,模型组(13.32±3.42)mkat/g,赤芍总苷3mg/kg组(16.74±2.76)mkat/g,赤芍总苷6mg/kg组(20.58±2.16)mkat/g,阳性药物组(18.12±4.98)mkat/g;Ca2+-ATPase活性:假手术组(15.00±2.40)mkat/g,模型组(7.32±1.44)mkat/g,赤芍总苷3mg/kg组(9.36±2.40)mkat/g,赤芍总苷6mg/kg组(13.26±1.98)mkat/g,阳性药物组(11.40±1.80)mkat/g,P<0.05～0.01]。结论:赤芍总苷可降低局灶性脑缺血再灌注大鼠大脑梗死面积百分比,抑制脂质过氧化反应,改善梗死后脑组织的能量代谢。

AIM： To investigate the protective effects and mechanism of total paeony glycoside （TPG） against focal cerebral ischemia/reperfusion injurY in rats. METHODS： The experiment was conducted in the Department of Physiology and Pharmacology, College of Basic Medical Science, Anhui Medical University between November 2005 and January 2006. 100 healthy Wister rats were randomly divided into 5 groups with 20 rats in each group： sham operation grouμ model grouμ 3 and 6 mg/kg TPG groups and positive drug group （intragastrically infused breviscapine）. The latter 3 groups were infused corresponding drugs respectively with 5 mL/kg body mass, once daily for 6 days. The sham operation group and model group were infused matching normal saline respectively. Models of focal cerebral ischemiareperfusion were prepared with intraluminal thread approach. The infarction area of brain tissue （percentage of infarction=infarction focus weight/ right cerebral hemisphere weight×100%）, malonaldehyde （MDA） content, lactate dehydrogenase （LDH）, Na^±-K^±-ATPase and Ca^2±-ATPase activity were examined after 2-hour of occlusion followed by 24-hour reperfusion. RESULTS： All the 100 rats were involved in the result analysis. ①Percentage of infracted area in brain tissue： Compared with the model grouμ the 3 and 6 mg/kg TPG groups and positive drug group were decreased [model group： （27.4±3.3）%, 3 mg/kg TPG group： （23.3±3.6）%, 6 mg/kg TPG group： （18.2±5.3）%, positive drug group： （19.3±4,1）%, P 〈 0.05-0.01]. ②Content of MDA and LDH in brain tissue： Compared with the sham operation grouμ the content of MDA in the model group was increased, the LDH activity was decreased; compared with the model grouμ 3 and 6 mg/kg TPG and positive drug groups could decrease the content of MDA, and enhance the LDH activity [content of MDA： sham operation group （2.11±0.32） μmol/g, model group （7.43±1.24） μmol/g, 3 mg/kg TPG （3.14±0.77） μmol/g, 6mg/kg TPG （2.54±1.08） μmol/g, positive drug group （2.86±0.83） μ mol/g; LDH activity： sham opeeration group （55.84 ±3.50） μ kat/g, model group （20.50±2.17） μ kat/g, 3 mg/kg TPG （28.01 ±5.83） μkat/g, 6 mg/kg TPG （44.34±4.50） μkat/g, positive drug group （34.01±5.17） μkat/g, P 〈 0.05-0.01]. ③Na^＋-K^＋-ATPase and Ca^2＋- ATPase activity in brain tissue： Compared with the sham operation grouμ the activity in the model group was decreased; compared with the model grouμ 3 and 6 mg/kg TPG and positive drug groups were increased [Na^＋- K^＋-ATPase activity： sham operation group （21.54±4.98） mkat/g, modelgroup （13.32±3.42） mkat/g, 3 mg/kg TPG （16.74±2.76） mkat/g, 6 mg/kg TPG （20,58±2.16） mkat/g, positive drug group （18.12±4.98） mkat/g; Ca^2＋- ATPase activity： sham operation group （15.00±2.40） mkat/g, model group （7.32±1.44） mkat/g, 3 mg/kg TPG （9.36±2.40） mkat/g, 6 mg/kg TPG （13.26±1.98） mkat/g, positive drug group （11.40±1.80） mkat/g, P 〈 0.05-0.01]. CONCLUSION： TPG can improve the energy metabolism of the brain tissue after infarction by decreasing the cerebral infracted area and inhibiting the peroxidatie reaction of lipid.