[1]梁智雄　彭　岩　胡　松.预防性应用辛伐他汀对大鼠脑出血后血肿体积和神经功能的影响[J].中国临床神经外科杂志,2018,(05):331-334.[doi:10.13798/j.issn.1009-153X.2018.05.009]
　LIANG Zhi-xiong,HU Song,PENG Yan..Effects of prophylactic application of simvastatin on hematoma volume and neurological function in rats with intracerebral hemorrhage[J].,2018,(05):331-334.[doi:10.13798/j.issn.1009-153X.2018.05.009]
点击复制

预防性应用辛伐他汀对大鼠脑出血后血肿体积和神经功能的影响()
分享到：

《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2018年05期
页码:
331-334
栏目:
论著
出版日期:
2018-05-25

文章信息/Info

Title:
Effects of prophylactic application of simvastatin on hematoma volume and neurological function in rats with intracerebral hemorrhage
文章编号:
1009-153X（2018）05-0331-04
作者:
梁智雄　彭　岩　胡　松
作者单位：430050，武汉市第五医院重症医学科（梁智雄、胡　松、彭岩）
Author(s):
LIANG Zhi-xiong;  HU Song;  PENG Yan.
Department of Critical Care Medicine, The Fifth Hospital of Wuhan City, Wuhan 430050, China
关键词:
脑出血; 脑水肿; 神经功能; 预防性应用; 辛伐他汀; 大鼠
Keywords:
Prophylactic application;  Simvastatin;  Intracerebral hemorrhage;  Brain edema;  Neurological function;  Rats
分类号:
R 743.34
DOI:
10.13798/j.issn.1009-153X.2018.05.009
文献标志码:
A
摘要:
目的 探讨预防性应用辛伐他汀对大鼠脑出血后血肿体积及神经功能的影响。方法 将96只雄性成年SD大鼠随机分为对照组（n=24）、脑出血组（n=24）、高剂量辛伐他汀组（HS组，n=24）和低剂量辛伐他汀组（LS组，n=24）。采用Ⅶ型胶原酶注射法建立大鼠ICH模型，对照组注入1 μl生理盐水。辛伐他汀干预组造模前2周给予辛伐他汀灌胃至造模当天（LS组2 mg/kg·d，HS组8 mg/kg·d）。造模前检测血清总胆固醇（TC）、低密度脂蛋白胆固醇 （LDL-C）水平；造模后24 h，每组取6只大鼠测定血肿体积；造模后5 d，每组取6只大鼠评估肢体运动功能，然后采用干/湿重法检测脑含水量；造模后5 d，每组取6只大鼠采用FluoroJade B染色检测血肿周围神经元变性；造模后5 d，每组取6只大鼠采用western blot检测血肿周围脑组织血管内皮生长因子（VEGF）、水通道蛋白（AQP）4、磷酸化胞外信号调节激酶（p-ERK）和磷酸化c-Jun 氨基末端激酶（p-JNK）表达。结果 与对照组相比，脑出血组血肿体积显著增加（P<0.05），脑含水量、血肿周围脑组织FJB阳性细胞数以及VEGF、AQP4、p-ERK和p-JNK表达水平均明显增高（P<0.05），神经功能显著变差（P<0.05）。预防性应用辛伐他汀，显著缩小血肿体积（P<0.05），显著降低脑含水量、血肿周围脑组织FJB阳性细胞数以及VEGF、AQP4、p-ERK和p-JNK表达水平（P<0.05），显著改善大鼠神经功能（P<0.05）。HS组血清TC和LDL-C水平、神经功能、血肿周围VEGF、AQP4、p-ERK和p-JNK表达水平较LS组显著改善（P<0.05），但两组血肿体积、脑含水量、血肿周围变性神经元数量均无统计学差异（P>0.05）。结论 预防性应用辛伐他汀可能通过抑制VEGF和AQP4的表达，减轻血肿周围脑组织水肿，减少血肿周围神经元变性，从而改善大鼠脑出血后神经功能。
Abstract:
Objective To investigate the effects of prophylactic application of simvastatin on hematoma volume and neurological function in the rats with intracerebral hemorrhage (ICH). Methods Ninety-six male SD rats were randomly divided into 4 groups of 24 animals each, i.e., control, ICH, high dose simvastatin (HS) and low dose simvastatin (LS) groups. The rats received oral administration of simvastatin for 2 weeks before ICH was established in both the HS and LS groups. The serum lipid levels and hematoma volume were measured 24 hours after ICH. The neurological function and water content of brain tissues were determined 5 days after ICH in 6 rats of each group. The neuronal degeneration in 6 rats of each group and expression of vascular endothelial growth factor (VEGF), aquaporin 4 (AQP4), phosphorylated exracellular signal regulated kinase (p-ERK) and phosphorylated c-Jun amino-terminal kinase (p-JNK) in the perihematomal tissues were determined by FluoroJade B (FJB) staining and western blot 5 days after ICH, respectively. Results The serum lipid levels, water content of brain tissues and expression levels of VEGF, AQP4, p-ERK and p-JNK were significantly higher in the ICH group than LS group (P<0.01) which were significantly higher than HS group (P<0.01). The neurological function was significantly better in HS group than LS group (P<0.05), which was significantly better than ICH group (P<0.05). The number of FJB-positive cells was significantly less in HS and LS groups than ICH group. There was no significant difference in the hematoma volume among ICH, HS and LS groups 24 hours after ICH (P>0.05). There was no significant difference in the number of FJB-positive cells between HS and LS groups (P>0.05). Conclusion Prophylactic application of simvastatin attenuates neurologic defect probably by up-regulating VEGF and AQP4 expressions in the perihematomal tissues and reducing perihematomal edema in rats with ICH.

参考文献/References:

[1] Feher A, Pusch G, Koltai K, et al. Statin therapy in the pri- mary and the secondary prevention of ischaemic cerebro- vascular diseases [J]. Int J Cardiol, 2011, 148(2): 131-138.
[2] Scheitz JF, MacIsaac RL, Abdul-Rahim AH, et al. Statins and risk of poststroke hemorrhagic complications [J]. Neu- rology, 2016, 86(17): 1590-1596.
[3] Ni W, Mao S, Xi G, et al. Role of erythrocyte CD47 in intra- cerebral hematoma clearance [J]. Stroke, 2016, 47(2): 505- 511.
[4] Okauchi M, Hua Y, Keep RF, et al. Deferoxa mine treat- ment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration [J]. Stroke, 2010, 41(2): 375-382.
[5] Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis [J]. J Neurol Psychiatry, 2014, 85 (6): 660-667.
[6] McFarland AJ, Anoopkumar-Dukie S, Arora DS, et al. Molecular mechanisms underlying the effects of statins in the central nervous system [J]. Int J Mol Sci, 2014, 15(11): 20607-20637.
[7] Mihos CG, Pineda AM, Santana O. Cardiovascular effects of statins, beyond lipid-lowering properties [J]. Pharmacol Res, 2014, 88: 12-19.
[8] Goldstein LB, Amarenco P, Zivin J, et al. Statin treatment and stroke outcome in the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial [J]. Stroke, 2009, 40(11): 3526-3531.
[9] Tapia Perez JH, Yildiz OC, Schneider T, et al. Meta- analysis of statin use for the acute therapy of spontaneous intracerebral hemorrhage [J]. J Stroke Cerebrovasc Dis, 2015, 24(11): 2521-2526.
[10] Konishi M, Iso H, Komachi Y, et al. Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries [J]. Stroke, 1993, 24(7): 954-964.
[11] Laufs U, Gertz K, Huang P, et al. Atorvastatin upregulates typeⅢ nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice [J]. Stroke, 2000, 31(10): 2442- 2449.
[12] Rite I, Machado A, Cano J, et al. Intracerebral VEGF injection highly upregulates AQP4 mRNA and protein in the perivascular space and glia limitans externa [J]. Neurochem Int, 2008, 52(4-5): 897-903.
[13] Qi LL, Fang SH, Shi WZ, et al. CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes [J]. Life Sci, 2011, 88(1-2): 50-56.
[14] Kobayashi H, minami S, Itoh S, et al. Aquaporin subtypes in rat cerebral microvessels [J]. Neurosci Lett, 2001, 297(3): 163-166.
[15] Tang Y, Wu P, Su J, et al. Effects of aquaporin-4 on edema formation following intracerebral hemorrhage [J]. Exp Neurol, 2010, 223(2): 485-495.
[16] Sahebkar A, Ponziani MC, Goitre I, et al. Does statin therapy reduce plasma VEGF levels in humans: a systematic review and meta-analysis of randomized controlled trials [J]. Meta- bolism, 2015, 64(11): 1466-1476.

相似文献/References:

[1]郑　涛　赵兰夫　高国栋.多囊肾尿毒症期并发脑出血综合治疗1例[J].中国临床神经外科杂志,2016,(05):320.[doi:10.13798/j.issn.1009-153X.2016.05.024]
[2]孔令舜　刘玉光.钻孔引流术治疗阿司匹林相关幕上脑出血的效果与安全性[J].中国临床神经外科杂志,2016,(03):181.[doi:10.13798/j.issn.1009-153X.2016.03.019]
[3]皮水平　刘　杰　黄前樟.长期服用抗凝药物的老年颅脑损伤患者治疗体会[J].中国临床神经外科杂志,2016,(02):117.[doi:10.13798/j.issn.1009-153X.2016.02.022]
[4]张　源　王文浩　林　洪　林俊明　黄　巍　李　君　罗　飞　胡连水.侧脑室后角穿刺术的新方法介绍[J].中国临床神经外科杂志,2016,(01):26.[doi:10.13798/j.issn.1009-153X.2016.01.009]
[5]陈　进　徐绪卿　祝　斐　金卫星　路　遥.白蛋白联合呋塞米降低颅脑损伤患者颅内压的临床观察[J].中国临床神经外科杂志,2015,(12):757.[doi:10.13798/j.issn.1009-153X.2015.12.019]
[6]谢　敏　周小炫 综述　吴成翰 审校.Toll样受体4与脑出血的研究进展[J].中国临床神经外科杂志,2015,(01):55.[doi:10.13798/j.issn.1009-153X.2015.01.019]
[7]韦向亮　李　皿　庞继彦　赵　东.早期高压氧治疗对急性脑出血患者脑水肿和血清氧化应激产物水平的影响[J].中国临床神经外科杂志,2016,(09):563.[doi:10.13798/j.issn.1009-153X.2016.09.019]
[8]王洪流,张爱明,董又坤.同时发生的双侧基底节区出血1例[J].中国临床神经外科杂志,2016,(11):736.[doi:10.13798/j.issn.1009-153X.2016.11.033]
[9]罗　明　段发亮　吴京雷　闵　强　陈晓斌　黄乔春　杨国平.神经导航下内镜手术治疗不典型自发性脑出血14例[J].中国临床神经外科杂志,2017,(01):40.[doi:10.13798/j.issn.1009-153X.2017.01.015]
[10]张如梦　王轶群　陈　甲　薛东章　杨世泉　魏学志　程晋成.脑出血抗栓药物应用研究进展[J].中国临床神经外科杂志,2017,(12):860.[doi:10.13798/j.issn.1009-153X.2017.12.022]

备注/Memo

备注/Memo:
通讯作者：胡　松，E-mail：Husong919@163.com
更新日期/Last Update: 2018-04-25