摘要
目的研究荭草苷对脑缺血再灌大鼠的神经保护作用及其作用机制。方法按照体重将大鼠随机分为5组,每组15只:假手术组、模型组、对照组和实验I、II组。除了假手术组以外,其余各组用线栓法建立大鼠局灶性脑中动脉阻断(MCAO)模型。术后0,12 h,对照组和2个实验组均腹腔注射荭草苷溶液2.9 mg·m L^(-1),假手术组和模型组给予等剂量0.9%Na Cl。此外,术前0.5,24h,实验I组给予西罗莫司2.24 mg·m L^(-1),实验II组给予3-甲基腺嘌呤(3-MA)3.0 mg·m L^(-1),其余各组给予相同剂量0.9%Na Cl。脑缺血再灌24 h,进行神经功能评分,以2,3,5-氯化三苯基四氮唑(TTC)法观察大鼠脑梗死体积,以蛋白免疫印迹观察缺血侧脑内自噬相关蛋白Beclin1与微管相关蛋白轻链3(LC3)的表达情况。结果模型组的脑梗死体积为(36.63±2.06)%,高于假手术组(0.67±0.12)%,差异有统计学意义(P<0.01);对照组和实验I、II组的脑梗死体积分别为(14.71±1.63)%,(25.22±1.58)%,(6.45±1.07)%,给药组与模型组比较,差异均有统计学意义(均P<0.05)。自噬相关蛋白Beclin1的相对表达:模型组、假手术组、对照组和实验I、II组分别为3.16±0.17,1.00±0.06,1.67±0.15,2.24±0.13,1.21±0.09;自噬相关蛋白LC3的相对表达,这5组分别为2.98±0.12,1.00±0.05,1.54±0.13,2.24±0.12,1.49±0.17。模型组与假手术组比较,上述指标差异均有统计学意义(均P<0.01);对照组和实验组与模型组比较,给药后差异均有统计学意义(均P<0.05);实验I组与对照组比较,上述指标差异均有统计学意义(均P<0.05)。结论荭草苷对脑缺血再灌大鼠的神经保护作用可能是通过抑制自噬作用来实现的。
Objective To explore the neuroprotective effects of orientin in rats after cerebral ischemia - reperfusion and its possible mechanisms. Methods SD male rats were randomly divided into five groups, with 15 rats in each group：sham group, m6del group, control group, experimen- tal I group, experimental II group Middle cerebral artery occlusion （MCAO） model was established by suture method in each group except sham group. For sham group, separate the carotid artery only. The 2.9 mg· mL-1 of orientin was administrated at 0 h and 12 h of reperfusion in control group and two experimental groups. At 0. 5, 24 h before the opera- tion, autophagy inducer （rapamycin 2. 24 mg · mL-1） and autophagy inhibitor E 3 - methyladenine （ 3 - MA） 3.0 mg· mL- 1 ] were adminis- trated in experimental I group and experimental II group, respectively. The same dosage of normal saline was administrated to other groups. The neurological deficit scores were evaluated and brain infarct volume was determined by 2,3,5 -triphenyhetrazolium chlo- ride （TYC） staining after 24 h of reperfusion. Moreover, protein immunoblotting was used to observe the protein levels of Beclinl and microtubule -associated proteinl light chain3 （LC3）. Results The brain infarct volume in model group was （36.63 ± 2. 06）%, which was higher than sham group （0. 67 ±0. 12）%, the difference was statistically significant （P 〈0. 01 ）. The brain infarct volume in control group, experimental I and II group were （14. 71± 1.63）%, （25.22 ± 1.58）% and （6.45 ± 1.07）%, respectively; compared with model group and three drugs groups, the difference were statistically significant （all P 〈0. 05 ）. The expression of autophagy protein Beclinl （APB） in model group, sham group were 3. 16 ＋0. 17, （ 1.00 ±0. 06） while control group, experimental I and II groups were, 1.67 ±0. 15, 2.24 ±0. 13 and 1.21±0. 09, respectively. For the protein expression of LC3 in model group, sham group, control group, experimental I and II groups were 2. 98 ± 0. 12, 1.00 ±0. 05, 1.54±0. 13,2.24± 0. 12, 1.49±0. 17. Compared with sham group and model group, the difference were statistically significant （all P 〈 0. 01 ）. Compared with model group and three drugs groups, the difference were statistically significant （ all P 〈 0. 05）. Compared with control group and experimental I group, the difference of the protein expression were statistically significant （all P 〈 0.05 ）. Conclusion The neuroprotective effects of orientin in rats after cerebral ischemia - reperfusion may be mediated through inhibition of autophagy.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第5期565-568,共4页
The Chinese Journal of Clinical Pharmacology
基金
河北北方学院重大基金资助项目(ZD1314)
河北省研究生创新基金资助项目(2015-203
2016-288)
关键词
荭草苷
脑缺血再灌
自噬
神经保护作用
orientin
cerebral ischemia - reperfusion
autophagy
neuroprotective
