淫羊藿苷对大鼠脑缺血-再灌注损伤的保护作用及机制研究
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摘要
目的观察淫羊藿苷(ICA)对大鼠脑缺血-再灌注损伤的保护作用并探讨其机制。方法 SD大鼠40只,随机分为假手术组、模型组、ICA低剂量组(30 mg/kg)和ICA高剂量组(80 mg/kg),每组10只。造模前假手术组、模型组予同体积0.9%氯化钠注射液,ICA高、低剂量组分别腹腔注射80、30 mg/kg剂量的ICA 2 m L。给药7 d后,采用颈总动脉夹闭法制备脑缺血-再灌注损伤模型。缺血0.5 h后,再灌注24 h分别检测缺血脑组织谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、髓过氧化物酶(MPO)活性、一氧化氮(NO)含量和一氧化氮合酶(NOS)活性;采用酶联免疫吸附测定(ELISA)法检测脑组织肿瘤坏死因子-α(TNF-α)和血清白细胞介素-1β(IL-1β)的含量。结果脑缺血-再灌注24 h后与假手术组比较,模型组GSH-Px、SOD活性值差异有统计学意义(P <0.01);与模型组比较,ICA低剂量组和ICA高剂量组大鼠脑组织GSH-Px、SOD活性明显增高,差异有统计学意义(均P <0.01)。与假手术组比较,模型组MDA含量、MPO活性、NO含量、NOS活性、TNF-α含量、血清IL-1β含量差异有统计学意义(P <0.01);与模型组比较,ICA低剂量组和ICA高剂量组大鼠脑组织MDA含量、MPO活性、NO含量、NOS活性、TNF-α含量、血清IL-1β含量明显减低,差异有统计学意义(均P <0.01)。结论 ICA对大鼠脑缺血-再灌注损伤具有神经保护作用,其机制可能与增高GSH-Px、SOD活性、降低MDA含量,抑制自由基损伤;降低NO含量、NOS活性,抑制神经毒性损伤;降低MPO活性、TNF-α、IL-1β含量抑制炎症反应损伤有关。
Objective: To explore the protective effects and mechanism of Icariin on cerebral ischemia-reperfusion injury in rats. Methods: 40 SD rats were divided into the sham operation group,the model group,Icariin low-dose group,Icariin high-dose group. Cerebral ischemia-reperfusion model was established with carotid artery clamping method. GSH-Px activity,SOD activity and MDA contents,MPO activity,NO contents,NOS activity were measured in the 24 th hour after the cerebral reperfusion post 0.5 h ischemia. The contents of TNF-α and IL-1β were detected by ELISA. Results: In the 24 th hour after the cerebral ischemia-reperfusion,compared with the sham operation group,the model group had significant difference in GSH-Px and SOD activity,MDA content,MPO activity,NO content,NOS activity,TNF-α content and serum IL-1β content(P < 0.01). Compared with the model group,the activity of GSH-Px and SOD increased significantly,and MDA content,MPO activity,NO content,NOS activity,TNF-α content and serum IL-1β content decreased significantly in ICA groups,with significant difference(P < 0.01). Conclusion: ICA has neuroprotective effect on cerebral ischemia-reperfusion injury in rats.Its mechanism may be related to increasing GSH-Px and SOD activity,decreasing MDA content,inhibiting free radical damage,reducing NO content and NOS activity,inhibiting neurotoxic damage,reducing MPO activity and the contents of TNF-α and IL-1β,and inhibiting inflammation damage.
Objective: To explore the protective effects and mechanism of Icariin on cerebral ischemia-reperfusion injury in rats. Methods: 40 SD rats were divided into the sham operation group,the model group,Icariin low-dose group,Icariin high-dose group. Cerebral ischemia-reperfusion model was established with carotid artery clamping method. GSH-Px activity,SOD activity and MDA contents,MPO activity,NO contents,NOS activity were measured in the 24 th hour after the cerebral reperfusion post 0.5 h ischemia. The contents of TNF-α and IL-1β were detected by ELISA. Results: In the 24 th hour after the cerebral ischemia-reperfusion,compared with the sham operation group,the model group had significant difference in GSH-Px and SOD activity,MDA content,MPO activity,NO content,NOS activity,TNF-α content and serum IL-1β content(P < 0.01). Compared with the model group,the activity of GSH-Px and SOD increased significantly,and MDA content,MPO activity,NO content,NOS activity,TNF-α content and serum IL-1β content decreased significantly in ICA groups,with significant difference(P < 0.01). Conclusion: ICA has neuroprotective effect on cerebral ischemia-reperfusion injury in rats.Its mechanism may be related to increasing GSH-Px and SOD activity,decreasing MDA content,inhibiting free radical damage,reducing NO content and NOS activity,inhibiting neurotoxic damage,reducing MPO activity and the contents of TNF-α and IL-1β,and inhibiting inflammation damage.
引文
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[11] P Bonnin,PL Leger,S Renolleau,et al. Dual action of No synthases on blood flow and infarct volume consecutive to neonatal focal cerebral ischemia[J]. Experimental Neurology,2012,236(1):50-57.
[12] Detopoulou P,Nomikos T,Fragopoulou E,et al. Platelet activating factor(PAF)and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure[J]. Clin Biochem,2009,42(1-2):44-49.
[13] TU XK,YANG WZ,SHI SS,et al. Spatio-temporal distribution of inflammatory reaction and expression of TLR2/4 signaling pathway in rat brain following permanent focal cerebral ischemia[J]. Neurochem Res,2010,35(8):1147-1155.
[14] Xing B,Chen H,Zhang M,et al. Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat[J]. Stroke,2008,39(8):2362-2369.
[15] Kang GH,Yan BC,Cho GS,et al. Neuroprotective effect of fucoidin on lipopolysaccharide accelerated cerebral ischemic injury through inhibition of cytokine expression and neutrophil infiltration[J]. Journal of the Neurological Sciences,2012,18(1-2):25-30.
[16]董海平,周薇,王震虹,等.右美托咪啶预处理经AMPK/SIRT1通路抑制大鼠脑缺血再灌注损伤的炎性反应[J].中国医药导报,2018,15(1):4-9.
[2]路宇仁,陈昳冰,崔元璐,等.淫羊藿苷药理作用研究进展[J].中国实验方剂学杂志,2018,24(17):209-219.
[3]胡吉梦,姜昊文.淫羊藿素及相关衍生物的抗肿瘤机制研究进展[J].上海中医药杂志,2018,52(4):107-112.
[4]任鹏宇,关亚新,张婷婷,等.西洋参茎叶皂苷对缺血再灌注损伤大鼠脑组织NO和NOS表达的影响[J].牡丹江医学院学报,2017,38(2):19-21.
[5]郭庆军,王桂敏,张秀秀.淫羊藿苷预处理对心肌缺血再灌注损伤炎症反应的影响[J].中国病理生理杂志,2013,29(11):2034-2038.
[6] Lian SL,Chen W,Raung SL,et al. Asscocication of immune responses and iseheinic brain infarction[J]. Neuroreport,2001,12(9):1943-1947.
[7]吴芹,陆远富,张锋,等.淫羊藿苷对自然衰老大鼠海马组织BDNF和TrkB mRNA表达的影响[J].中国新药与临床杂志,2013,32(7):548-551.
[8]刘松,刘超明,赖丽娟,等.淫羊藿素的药理作用研究进展[J].赣南医学院学报,2017,37(4):631-635.
[9] Reddy MK,Labhasetwar V. Nanoparticle-mediated delivery of superoxide dismutase to the brain:an effective strategy to reduce ischemia-reperfusion injury[J]. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology, 2009,23(5):1384-1395.
[10] Kikuchi K,Kawahara K,Tancharoen S,et al. The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells[J]. J Pharmacol Exp Ther,2009,329(3):865-874.
[11] P Bonnin,PL Leger,S Renolleau,et al. Dual action of No synthases on blood flow and infarct volume consecutive to neonatal focal cerebral ischemia[J]. Experimental Neurology,2012,236(1):50-57.
[12] Detopoulou P,Nomikos T,Fragopoulou E,et al. Platelet activating factor(PAF)and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure[J]. Clin Biochem,2009,42(1-2):44-49.
[13] TU XK,YANG WZ,SHI SS,et al. Spatio-temporal distribution of inflammatory reaction and expression of TLR2/4 signaling pathway in rat brain following permanent focal cerebral ischemia[J]. Neurochem Res,2010,35(8):1147-1155.
[14] Xing B,Chen H,Zhang M,et al. Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat[J]. Stroke,2008,39(8):2362-2369.
[15] Kang GH,Yan BC,Cho GS,et al. Neuroprotective effect of fucoidin on lipopolysaccharide accelerated cerebral ischemic injury through inhibition of cytokine expression and neutrophil infiltration[J]. Journal of the Neurological Sciences,2012,18(1-2):25-30.
[16]董海平,周薇,王震虹,等.右美托咪啶预处理经AMPK/SIRT1通路抑制大鼠脑缺血再灌注损伤的炎性反应[J].中国医药导报,2018,15(1):4-9.