盐酸戊乙奎醚（长托宁）抑制脑缺血／再灌注时谷氨酸的释放及受体机制研究

目的：观察盐酸戊乙奎醚对全脑缺血／再灌注大鼠易损区海马谷氨酸（Glu）及其受体（NMDAR1）的影响,探讨盐酸戊乙奎醚脑保护作用机制。方法：雄性Wistar大鼠60只,随机分为3组（n=20）：假手术组（A组）;缺血再灌注对照组（B组）;盐酸戊乙奎醚干预组,采用Pulsinelli-Brierley四血管阻断法制备全脑缺血模型,实验分两部分进行,各组随机选择10只大鼠于全脑缺血15min再灌注1h、3h、6h,采用脑微透析技术结合高效液相色谱（HPLC）检测大鼠海马细胞外Glu水平的变化,其余10只大鼠于再灌注3h后灌流固定断头取脑,采用免疫组织化学方法,检测海马CA1区NMDAR1蛋白表达。结果：与缺血／再灌注组各对应时点相比较,盐酸戊乙奎醚干预组大鼠海马细胞外Glu含量明显降低,统计结果差异均有显著性（P〈0．05或P〈0．01）;海马CA1区NMDAR1表达明显受抑制,积分光密度、阳性细胞面积、平均灰度值均存在显著性差异（P〈0．05或P〈0．01）。结论：脑缺血／再灌注早期应用盐酸戊乙奎醚不仅减少兴奋性氨基酸释放,还能抑制NMDAR1的高表达而产生脑保护作用。     

一氧化氮、内皮素-1对大鼠肢体缺血/再灌注后脑损伤的影响

目的: 研究一氧化氮(NO)和内皮素-1(ET-1)在大鼠肢体缺血/再灌注(LI/R)后脑损伤中的作用,探讨NO/ET-1平衡关系的变化对脑损伤的影响.方法: 在大鼠LI/R损伤模型上,应用NO合成前体物质L-精氨酸(L-Arg)、一氧化氮合酶(NOS)抑制剂氨基胍(AG)、ETA受体阻断剂BQl23进行干预,观察血浆 NO、ET-1、MDA、XOD、SOD、LDH及脑组织tNOS、iNOS、cNOS、NO、ET-1、MDA、XOD、MPO、 SOD的变化.结果: 与对照组比较,I/R组血浆MDA、XOD、LDH及脑组织MDA、XOD、MPO升高,SOD活性降低(P<0.01),脑组织tNOS和iNOS明显升高,而cNOS明显降低(P<0.01),I/R组血浆及脑组织NO、ET-1增加,NO/ET-1比值降低,脑损伤加重.应用L-Arg及BQ123后,血浆及脑组织NO/ET-1比值较I/R组升高,脑损伤减轻,应用AG后,NO/ET-1比值降低,脑损伤进一步加重.结论: 肢体缺血/再灌注后,一氧化氮与内皮素-l的比值降低时脑损伤加重.     

雌激素对去卵巢大鼠离体心脏缺血／再灌注损伤的保护作用

目的：探讨雌激素对去卵巢大鼠离体心脏缺血／再灌注损伤的保护作用。方法：成年SD雌鼠,随机分为假手术组（Sham）,双侧卵巢切除组（Ovx）和双侧卵巢切除后补充17β-雌二醇组（Ovx＋E2）。各组离体心脏再随机分为不同时间的缺血再灌注亚组。测量的指标包括冠脉流出液中LDH及CK含量、心室肌细胞存活率及产率、基础状态和异丙肾上腺素（ISO）刺激状态下收缩幅度。结果：30min缺血及其各复灌纽均显著增加冠脉流出液中LDH、CK的释放量。Ovx组LDH、CK漏出在30min缺血及再灌注条件下,显著高于正常灌注组,而Ovx＋E2组可减轻心肌损伤,减少LDH、CK的释放。10min和20min缺血对心肌细胞存活率、产率及冠脉流出液中LDH、CK含量影响均不明显。Sham、Ovx、Ovx＋E2各组心肌细胞基础收缩幅度在正常和10minⅠ＋30minR灌注条件下无显著差异。Ovx显著增加其他各组心肌细胞基础收缩和ISO刺激收缩幅度,Ovx＋E2可使其降至Sham水平。结论：雌激素对去卵巢大鼠心肌缺血／再灌注损伤具有保护作用。     

The protective effect of oxytocin on renal ischemia/reperfusion injury in rats

AIM: Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study was to evaluate the protective role of oxytocin (OT) in protecting the kidney against ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Wistar albino rats (250-300 g) were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (1 mg/kg, ip) or vehicle was administered 15 min prior to ischemia and was repeated immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in renal tissue samples was monitored by chemiluminescence technique using luminol and lucigenin probes. RESULTS: The results revealed that I/R injury increased (p<0.01-0.001) serum urea, creatinine, TNF-alpha and LDH levels, as well as MDA, MPO and reactive oxygen radical levels in the renal tissue, while decreasing renal GSH content. However, alterations in these biochemical and histopathological indices due to I/R injury were attenuated by OT treatment (p<0.05-0.001). CONCLUSIONS: Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects renal tissue against I/R-induced oxidative damage.     

Changes of phospholipid composition and superoxide dismutase activity during global brain ischemia and reperfusion in rats

Alterations in phospholipid content and Cu/Zn superoxide dismutase (SOD) activity were examined in rat brain after 15 min of global ischemia (four-vessel occlusion) followed by 2-, 24- or 48-h reperfusion. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE), the main brain phospholipids, were markedly decreased in ischemic rats and remained decreased during the whole reperfusion period. Concentrations of phosphatidylinositol (PI) and sphingomyelin (SM) were also significantly reduced during ischemia but recovered during reperfusion period. In contrast, phosphatidylserine (PS) and lysophospholipids (LysoPL) were unchanged during ischemia but were elevated after 24 h of reperfusion. Significant reductions in blood plasma phospholipids were also demonstrated. 24-48 h of reperfusion markedly decreased PE, PC and PS contents, while the concentrations were almost unchanged by ischemia alone. Brain SOD activity decreased significantly during ischemia and was recovered to control value already after 2 h of reperfusion. These results suggest that ischemia/reperfusion is accompanied by a significant and selective degradation of brain phospholipids that may be attributable to oxidative stress and activation of phospholipases.     

参附注射液对大鼠全脑缺血/再灌注损伤的保护作用

目的:探讨参附注射液对大鼠全脑缺血/再灌注损伤的保护作用及其机制。方法:将SD雄性大鼠40只,随机分为4组(n=10):假手术组、模型对照组、尼莫地平组(30 mg/kg)和参附注射液组(10 mg/kg)。采用Pulsinelli’s四动脉阻断法造成全脑缺血/再灌注损伤模型(CI/R),分别于手术前1 d,术前1 h和再灌注前30 min给药,共3次。分别用高效液相色谱法测定脑组织谷氨酸(Glu)、天冬氨酸(Asp)和甘氨酸(Gly)含量,原子吸收分光光度测定Ca2+含量,干湿重法测定脑组织含水量,化学比色法测定脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与假手术组比较,CI/R模型组大鼠脑组织Glu、Ca2+、MDA含量和含水量明显升高(P<0.05,P<0.01),SOD活性明显降低(P<0.05);参附注射液能显著降低脑组织Glu、Ca2+含量和含水量(P<0.05,P<0.01),显著升高SOD活性及SOD/MAD比值(P<0.05)。结论:参附注射液防治脑缺血/再灌注损伤的机制与降低兴奋性氨基酸(EAA)毒性、阻滞Ca2+超载和提高抗氧化能力有关。     

Neuroprotective effects of valproic acid following transient global ischemia in rats

AimsA growing number of studies demonstrate that valproic acid (VPA), an anti-convulsant and mood-stabilizing drug, is neuroprotective against various insults. This study investigated whether treatment of ischemic stroke with VPA ameliorated hippocampal cell death and cognitive deficits. Possible mechanisms of action were also investigated.Main methodsGlobal cerebral ischemia was induced to mimic ischemia/reperfusion (I/R) damage. The pyramidal cells within the CA1 field were stained with cresyl violet. Cognitive ability was measured 7 days after I/R using a Morris water maze. The anti-inflammatory effects of VPA on microglia were also investigated by immunohistochemistry. Pro-inflammatory cytokine production was determined using enzyme-linked immunosorbent assays (ELISA). Western blot analysis was performed to determine the levels of acetylated H3, H4 and heat shock protein 70 (HSP70) in extracts from the ischemic hippocampus.Key findingsVPA significantly increased the density of neurons that survived in the CA1 region of the hippocampus on the 7th day after transient global ischemia. VPA ameliorated severe deficiencies in spatial cognitive performance induced by transient global ischemia. Post-insult treatment with VPA also dramatically suppressed the activation of microglia but not astrocytes, reduced the number of microglia, and inhibited other inflammatory markers in the ischemic brain. VPA treatment resulted in a significant increase in levels of acetylated histones H3 and H4 as well as HSP70 in the hippocampus.SignificanceOur results indicated that VPA protected against hippocampal cell loss and cognitive deficits. Treatment with VPA following cerebral ischemia probably involves multiple mechanisms of action, including inhibition of ischemia-induced cerebral inflammation, inhibition of histone deacetylase (HDAC) and induction of HSP.     

Gender specific effect of progesterone on myocardial ischemia/reperfusion injury in rats

The study was designed to investigate the effect of progesterone and its gender based variation on myocardial ischemia/reperfusion (I/R) injury in rats. Adult Sprague Dawley rats were divided into vehicle treated reperfusion injury group male (I/R-M), female (I/R-F), ovariectomised (I/R-OVR) and progesterone treatment (I/R-M+PG, I/R-F+PG, I/R-OVR+PG) groups, respectively. I/R injury was produced by occluding the left descending coronary artery (LCA) for 1 h and followed by re-opening for 1 h. Progesterone (2 mg kg(-1) i.p.) was administered 30 min after induction of ischemia. Hemodynamic parameters (+/-dp/dt, MAP), heart rate, ST-segment elevation and occurrence of ventricular tachycardia (VT) were measured during the I/R period. The myocardial infarct area, oxidative stress markers, activities of myeloperoxidase (MPO) and creatine kinase (CK) were determined after the experiment along with the assessment of the effect on apoptotic activity by using DNA fragmentation analysis. Histological observations were carried out on heart tissue. Treatment with progesterone significantly (P<0.05) reduced infarct area, lipid peroxidation (LPO) level and activity of MPO in females (I/R-F+PG) as compared to ischemic females (I/R-F). Progesterone significantly (P<0.001, P<0.05) inhibited serum CK activity and incidences of VT in female rats. Superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels were significantly elevated (P<0.05) in I/R-F+PG group. Internucleosomal DNA fragmentation was less in I/R-F+PG group when compared to I/R-F group. The ischemic male and ovariectomised (I/R-M and I/R-OVR) counterparts did not show any significant change after progesterone treatment. In conclusion, the cardioprotective effect of progesterone on myocardial I/R injury induced damage is based on gender of the animal. The protective effect could be mediated by attenuation of inflammation and its possible interaction with endogenous estrogen.     

牛磺酸对大鼠肢体缺血/再灌注后肺组织损伤的保护作用

目的:观察大鼠肢体缺血再灌注(LIR)后肺组织形态学的变化及牛磺酸对其影响.方法:Wistar大鼠随机分为3组,对照组(control)、缺血/再灌注组(LIR)、牛磺酸 缺血/再灌注组(Tau LIR),各组动物通过大体、光镜和透射电镜观察肺组织形态学变化,并测定肺系数和肺通透指数及肺组织活性氧和MDA含量.结果:大鼠LIR后肺组织出现以肺泡毛细血管膜通透性增加为特征的组织细胞损伤,光镜下显示毛细血管扩张充血、血管周围间隙增大、肺泡腔中有大量蛋白渗出物,电镜下可见肺泡上皮细胞之间、毛细血管内皮之间的紧密连接松解;肺系数和肺通透指数升高;肺组织活性氧及MDA含量增加.提前给予外源性牛磺酸可使肺组织损伤变化减轻.结论:牛磺酸对大鼠LIR后肺损伤有保护作用,其保护机理之一与其抗氧化,保护细胞之间的紧密连接有关.     

维生素E在青年和老年大鼠肾脏缺血/再灌注损伤中的作用

目的:探讨维生素E(VE)在青年和老年大鼠肾缺血/再灌注损伤(RI/RI)中的作用。方法:采用夹闭双侧肾动、静脉45min后恢复血流的方法制作RI/RI模型,测定血清中尿素氮(BUN)、肌酐(Scr)、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、诱生型一氧化氮合酶(iNOS)浓度,免疫组化检测肾皮质热休克蛋白70(HSP70)表达。流式细胞术检测肾皮质细胞凋亡率。结果:缺血/再灌注(I/R)后BUN、Scr含量明显升高,老年I/R组MDA含量高于青年I/R组,SOD含量低于青年IR组,HSP70、NO以及肾皮质细胞凋亡率高于control组;VE可显著降低RI/RI大鼠BUN、Scr、MDA、iNOS水平,升高NO和SOD水平,增加HSP70的表达,降低肾皮质细胞凋亡率。结论:VE可通过促进肾组织HSP70的表达,增加NO和SOD水平,提高大鼠体内清除自由基的能力,从而对青、老年大鼠肾缺血/再灌注损伤(RI/RI)起到一定的保护作用。     

Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils

The beneficial effects of antioxidant nutrients, as well as complex plant extracts, in cerebral ischemia/reperfusion brain injury are well known. Mediterranean diet, rich in olive products, is associated with lower incidence of cardiovascular disease, cancer, inflammation and stroke. In this study, the possible neuroprotective effect of standardized dry olive leaf extract (OLE) is investigated for the first time. Transient global cerebral ischemia in Mongolian gerbils was used to investigate the OLE effects on different parameters of oxidative stress and neuronal damage in hippocampus. The biochemical measurements took place at different time points (80 min, 2, 4 and 24 h) after reperfusion. The effects of applied OLE were compared with effects of quercetin, a known neuroprotective plant flavonoid. Pretreatment with OLE (100 mg/kg, per os) significantly inhibited production of superoxide and nitric oxide, decreased lipid peroxidation, and increased superoxide dismutase activity in all time points examined. Furthermore, OLE offered histological improvement as seen by decreasing neuronal damage in CA1 region of hippocampus. The effects of applied OLE were significantly higher than effects of quercetin (100 mg/kg, per os). Our results indicate that OLE exerts a potent neuroprotective activity against neuronal damage in hippocampus after transient global cerebral ischemia, which could be attributed to its antioxidative properties.     

The protective effect of apelin on ischemia/reperfusion injury

Apelin is the endogenous ligand for the APJ, a member of the G protein coupled receptors family. Apelin/APJ system is widely distributed in central nervous system and peripheral tissues, especially in heart, lung and kidney. Apelin plays important physiological and pathological roles in cardiovascular system, immune system, neuroprotection, etc. This article outlines the protective effect of apelin on ischemia/reperfusion (I/R) injury. Apelin could activate multiple protective mechanisms to prevent heart, brain, liver and kidney I/R injury. Apelin/APJ system may be a promising therapeutic target for ischemic and other related diseases.     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

异丙酚对全脑缺血/再灌注大鼠海马iNOS表达的影响

目的观察异丙酚对全脑缺血/再灌注大鼠海马神经元诱导型一氧化氮合酶(iNOS)表达的影响,探讨异丙酚对迟发性脑神经元损伤保护作用机制。方法采用Pulsinelli-Brierley四血管阻断法制备全脑缺血模型。全脑缺血20min再灌注24h后断头取脑,采用Western blot方法检测大鼠海马iNOS的蛋白表达。结果与缺血/再灌注组相比较,异丙酚处理组大鼠海马iNOS蛋白表达明显降低,存活的神经元数目明显增加,统计结果差异均有显著性(P<0.05或0.01)。结论异丙酚通过抑制iNOS蛋白表达对大鼠脑迟发性神经元损伤起保护作用。     

细胞自噬在大鼠缺血/再灌注肺损伤中的调控作用

目的: 探讨细胞自噬在大鼠缺血/再灌注肺损伤中的作用。方法: 随机将40只SD大鼠分为5组(n=8),分别为 ① 假手术组(Sham组):只开胸3.5 h;② 缺血/再灌注组(I/R组):开胸夹闭肺门缺血0.5 h后再灌注3 h;③ 溶剂组(DMSO组):术前1 h腹腔注射DMSO溶液;④自噬激动剂组(Rap组):术前腹腔注射雷帕霉素溶液;⑤自噬抑制剂组(3-MA组):术前1 h腹腔注射3-MA溶液;后三组的其余操作同I/R组。实验结束后处死大鼠,取肺组织,记录并计算肺组织湿/干重比(W/D)、总肺含水量变化(TLW) ,光镜和电镜观察肺组织及细胞形态,计算肺泡损伤率(IAR),Western blot检测自噬相关蛋白的表达情况。结果: 相对于sham组,其余四组肺W/D、TLW、IAR均明显升高,自噬相关蛋白表达明显上升,p-AMPK、Beclin 1、LC3 II 蛋白明显增多,p-mTOR、p62蛋白明显减少(P＜0.05或P＜0.01),光镜下其余各组肺组织有不同程度的水肿渗出,肺泡结构紊乱,电镜下细胞超微结构损伤加重,部分可见自噬小体;与DMSO组相比,3-MA组肺W/D、TLW、IAR明显下降(P＜0.05或P＜0.01),自噬相关蛋白表达明显下降,肺间质水肿较轻,细胞渗出较少,细胞超微结构损伤减轻,未见自噬小体。而I/R、DMSO、Rap组的各项指标变化无统计学差异(P＞0.05)。结论: 肺缺血/再灌注可诱发细胞自噬增强,从而引起大鼠肺损伤。     

缺血预适应对大鼠肢体缺血/再灌注后小肠细胞凋亡的影响

目的：观察大鼠肢体缺血再灌注后小肠粘膜自由基及钙含量改变与细胞凋亡情况．以及缺血预适应对其变化的影响。方法：将雄性Wistar大鼠18只,随机分为对照（Control）组,缺血／再灌注（I／R）组和缺血预适应（IPC＋I／R）组,分别测定血浆和小肠组织超氧化物歧化酶（SOD）、黄嘌呤氧化酶（XOD）、丙二醛（MDA）的含量,小肠组织钙及线粒体钙含量;小肠组织的Bel-2和Bax蛋白的表达水平;检测小肠细胞凋亡情况。结果：肢体I／R后血浆和小肠粘膜SOD减少而XOD和MDA增加;小肠组织钙及线粒体钙含量增多;Bel-2蛋白表迭和Bax表达增多,但Bel-2／Bax比值降低;凋亡细胞增多。IPC减轻了I／R后引起的XOD、MDA含量的升高,并且增加了SOD的含量;减轻了组织和线粒体钙超载;Bel-2的表达则明显升高而Bax表达较I／R组明显减少,Bel-2／Bax比值升高;凋亡细胞减少。结论：肢体IR引起小肠粘膜自由基的增多,钙超栽,凋亡细胞增多;IPC可能通过减少自由基的产生及钙超载,抑制细胞凋亡而对肢体I／R继发的小肠功能损伤起保护作用。     

The effects of lycopene on hepatic ischemia/reperfusion injury in rats

There is a very little information about the protective effect of lycopene (LYC) against hepatic ischemia–reperfusion injury. The present study was designed to examine the possible protective effect of the strong antioxidant and anti-inflammatory agent, LYC, on hepatic ischemia/reperfusion injury. For this purpose, rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. LYC at the doses of 2.5 and 5 mg/kg body weight (bw) were injected intraperitoneally, 60 min prior to ischemia. Upon sacrification, hepatic tissue samples were used for the measurement of catalase (CAT) activity and malondialdehyde (MDA) levels. Also, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were assayed in serum samples. As a result of the use of LYC at the doses of 2.5 and 5 mg/kg bw; while improvements of the ALT, AST, LDH and MDA values were partial and dose-dependent, the improvement of CAT activity was total and dose-independent (p < 0.05). Our findings suggest that LYC has a protective effect against ischemia/reperfusion injury on the liver.     

L-丝氨酸对大鼠脑缺血/再灌注损伤保护作用时间窗的实验研究

目的：研究L-丝氨酸对大鼠脑缺血/再灌注损伤保护作用的时间窗,并对其作用机制进行初探。方法：SD雄性大鼠随机分为假手术组、对照组、L-丝氨酸3h治疗组、6h治疗组、12h治疗组、24h治疗组。采用大脑中动脉栓塞（MCAO）建立大鼠局灶性脑缺血模型,2h后拔出栓线形成再灌注,各组分别于术后相应的时间点给予L-丝氨酸200mg/kg腹腔注射2次,对照组注射等剂量的生理盐水,所有动物再灌注后48h观测神经行为学评分、脑梗死体积。另取假手术组、对照组、L-丝氨酸6h治疗组,分别测定MCAO后脑内超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量,炎症细胞因子TNF-α、IL-6水平以及观察细胞超微结构改变。结果：与对照组相比,术后3h、6h给予L-丝氨酸治疗能显著降低大鼠神经行为学评分,减少脑梗死体积（P〈0.01或P〈0.05）,12h仅能降低神经行为学评分（P〈0.05）,而24h与对照组间均无差异;L-丝氨酸能提高MCAO后脑内SOD活性,降低MDA以及TNF-α、IL-6的水平,同时改善细胞超微结构。结论：在一定时间窗内,L-丝氨酸对大鼠MCAO具有明显的神经保护作用,其机制可能与降低氧自由基损伤,减轻炎症反应有关。     

小檗碱对大鼠脑缺血/再灌注损伤的保护作用及免疫机制

目的:探讨小檗碱对大鼠脑缺血/再灌注损伤的保护作用及免疫机制。方法:50只SD大鼠随机分为假手术组(Sham group)、模型组(Model group)、小檗碱低剂量组(BBR-L,25 mg/kg)、小檗碱中剂量组(BBR-M,50 mg/kg)、小檗碱高剂量组(BBR-H,100 mg/kg),每组各10只。采用Longa线栓法建立脑缺血/再灌注大鼠模型,缺血2h后再灌注24 h处理。于造模成功2 h后灌胃给药,假手术组和模型组组按上述方法同体积给予生理盐水。给药24 h后,测定各组大鼠神经功能缺损程度评分及脑梗死率;采用ELISA法检测抗氧化酶SOD和GSH-Px的活性、细胞因子TNF-α、IFN-β、IL-6和NO的含量;采用流式细胞术检测CD4⁺、CD8⁺及CD4⁺/CD8⁺血清含量;进一步采用RT-qPCR与Western blot技术检测大鼠脑组织内NF-κB-NLRP3信号轴关键基因及蛋白的表达情况。结果:与假手术组比较,模型组大鼠神经功能缺损程度、脑梗死率均升高(P<0....