|
|
|
| Effect and mechanism reserch of Gabexate on cerebral ischemia reperfusion injury in rats |
| QIAO Jianxin1 LIU Xipeng1 LIU Ming1 WANG Jinghui1 GUAN Chaonan2 |
1.Department of Neurosurgery, the First Affiliated Hospital of Hebei North University, Hebei Province, Zhangjiakou 075000, China;
2.Department of Nuclear Medicine, the First Affiliated Hospital of Hebei North University, Hebei Province, Zhangjiakou 075000, China |
|
|
|
Abstract Objective To explore the effect and mechanism of Gabexate on cerebral ischemia reperfusion injury in rats. Methods A total of 125 experimental rats were selected to establish focal cerebral ischemia reperfusion model by modified thread occlusion method. All rats were divided into sham operation group, model group and Gabexate high, medium and low dose groups according to random number table method, with 25 rats in each group. Low, medium and high dose Gabexate groups were intervened by intraperitoneal injection of 25, 50 and 75 mg Gabexate, respectively. Sham operation group and model group were given the same volume of normal saline. The rats in each group were scored by blind method. The pathological changes of brain tissue and the apoptosis of nerve cells were observed. The activities of antioxidant enzymes, malondialdehyde (MDA), inflammatory factors, apoptosis related gene expression and related protein expression in brain tissue were determined. Results The neurological deficit score, glutathione peroxidase (GSH-Px), B cell lymphoma factor 2 (bcl-2) mRNA and nuclear factor kappa B (NF-κB) in model group were lower than those in sham operation group, the apoptosis rate of nerve cells, MDA, superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, water soluble protein (Bax) mRNA, caspase-3 and NF-κB in model group were higher than those in sham operation group, the differences were statistically significant (P < 0.05). The neurological deficit score, MDA, SOD, bcl-2 mRNA and NF-κB in medium and high dose Gabexate groups were higher than those in low dose Gabexate group, the apoptosis rate, GSH-Px, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB of medium and high dose Gabexate groups were lower than those of low dose Gabexate group, the differences were statistically significant (P < 0.05). The scores of neurological deficit, MDA, SOD, bcl-2 mRNA and NF-κB in high dose Gabexate group were higher than those in medium dose Gabexate group, the apoptosis rate, GSH-Px, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB of high dose Gabexate group were lower than those of medium dose Gabexate group, the differences were statistically significant (P < 0.05). The neurological deficit score, MDA, SOD, bcl-2 mRNA and NF-κB in Gabexate low, medium and high dose groups were higher than those in model group, the apoptosis rate of nerve cells, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB in Gabexate low, medium and high dose groups were lower than those in model group, the differences were statistically significant (P < 0.05). The level of GSH-Px in Gabexate low dose group was higher than that in model group, and the levels of GSH-Px in Gabexate middle and high dose groups were lower than those in model group, the differences were statistically significant (P < 0.05). Conclusion Gabexate can effectively reduce the pathological damage caused by cerebral ischemia reperfusion in rats, inhibit lipid oxidation reaction after reperfusion, play a protective role, and reduce the damage caused by inflammatory reaction. The above effects may be caused by inhibiting NF-κB signal pathway and increasing the activity of antioxidant enzymes, so as to reduce the inflammatory injury of brain tissue and the apoptosis of nerve cells.
|
|
|
|
|
|
[1] 陈雪莲，刘月明，张萍，等.甲磺酸加贝酯对大鼠深Ⅱ°烫伤创面愈合的影响[J].成都医学院学报，2020，15（2）：200-203.
[2] 姜萌，赵鹏.奥曲肽联合加贝酯治疗重症急性胰腺炎疗效及对患者血清细胞因子水平的影响[J].陕西医学杂志，2020，49（2）：212-215.
[3] 刘秋香，牛福玉，孙利峰，等.早期肠内营养联合加贝酯治疗老年急性胰腺炎的疗效[J].中国老年学杂志，2019， 39（12）：2915-2918.
[4] 王华光，郑芸颖，王诗卉，等.115例注射用甲磺酸加贝酯临床应用合理性评价[J].中国新药杂志，2019，28（1）：110-116.
[5] 罗文杰.加贝酯在重症急性胰腺炎患者治疗中的效果及对肠屏障功能的影响[J].湖南师范大学学报：医学版，2018，15（4）：138-140.
[6] 丛若尘，何伯圣.小肠缺血再灌注损伤机制的研究进展和防治策略[J].医学综述，2020，26（14）：2716-2721，2727.
[7] 董云，陈众，刘丹丹，等.经皮腔内球囊缺血后处理对肢体缺血再灌注损伤的保护作用[J].中国老年学杂志，2020，40（15）：3228-3230.
[8] 任鹏鹏，韩冲芳，李浩甲，等.PINK1-parkin途径及其与心肌缺血再灌注损伤的关系[J].医学研究杂志，2020，49（7）：179-182.
[9] 李翯，刘鹏，骆银，等.限制性再灌注对脑缺血再灌注损伤的保护作用[J].中国微侵袭神经外科杂志，2020，25（4）：177-180.
[10] 麦叶，顾勇.丁苯酞预处理对大鼠心肺复苏后脑缺血再灌注损伤的保护作用研究[J].中国临床药理学杂志，2020， 36（15）：2246-2249，2260.
[11] Lan X，Zhang X，Zhou GP，et al. Electroacupuncture reduces apoptotic index and inhibits p38 mitogen-activated protein kinase signaling pathway in the hippocampus of rats with cerebral ischemia/reperfusion injury [J]. Neural Regen Res，2017，12（3）：409-416.
[12] Xiong C，Zang X，Zhou X，et al. Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion [J]. Oncotarget，2017，8（19）：31238-31253.
[13] Bouslama M，Haussen DC，Grossberg JA，et al. Computed tomographic perfusion selection and clinical outcomes after endovascular therapy in large vessel occlusion stroke [J]. Stroke，2017，48（5）：1271-1277.
[14] Amber K，Mohmmad Y，Abdullah S，et al. Anticancer activity of novel gabexate mesilate mimetics in colorectal cancer cells [J]. Chemistry Select，2018，3（24）：6942-6948.
[15] Wang G，Liu Y，Zhou S，et al. Effect of somatostatin，ulinastatin and gabexate on the treatment of severe acute pancreatitis [J]. Am J Med Sci，2016，351（5）：506-512.
[16] 杨白婧，付高洁，李美姗，等.生长抑素、加贝酯联合乌司他丁治疗急性胰腺炎的临床疗效分析[J].世界复合医学，2020，6（2）：156-158.
[17] 贺旭，王伟，汤艳，等.神经保护剂在脑缺血后大脑神经再生中的作用[J].中国老年学杂志，2020，40（17）：3787-3790.
[18] 袁庆，殷孟兰，赵磊，等.注射用血栓通对脑缺血损伤的药理研究现状[J].中国临床药理学杂志，2020，36（16）：2521-2524.
[19] 薛玉梅，李晓兵，薛占苍，等.槐定碱对大鼠局灶性脑缺血损伤的保护作用[J].中国临床药理学杂志，2020，36（15）：2250-2253.
[20] 杨赫，唐强，陈秋欣.肠-脑轴在脑缺血中作用的研究进展[J].中国康复理论与实践，2020，26（7）：793-796.
[21] 周乃强，姚杨玲，黄坚毅.FOXO3a蛋白对脑缺血损伤大鼠细胞自噬的影响研究[J].中西医结合心脑血管病杂志，2020，18（15）：2422-2426.
[22] 徐琛，刘竞丽.脑缺血再灌注模型大鼠miR133b-3p表达及意义[J].江苏大学学报：医学版，2020，30（4）：326-329.
[23] 陈方，路凯，白宁，等.局灶性脑缺血-再灌注损伤模型大鼠中CELSR1、VEGF和TRPM7表达及异丙酚预处理效果分析[J].脑与神经疾病杂志，2020，28（9）：545-549.
[24] 马晓娇，承欧梅，校欢，等.急性脑缺血通过激活EphB2/ephrin-B1/NMDA受体信号通路促进小鼠海马神经发生[J].中国病理生理杂志，2020，36（8）：1389-1395. |
|
|
|
