阿霉素减轻坐骨神经慢性缩窄性损伤大鼠的神经病理性疼痛及其机制

目的观察阿霉素(DOX)对坐骨神经慢性缩窄性损伤(CCI)模型大鼠的镇痛作用,并从形态学及组织凋亡蛋白的角度对其机制进行分析。方法将SD大鼠随机分为4组:假手术组(Sham)、CCI模型组(Model)、假手术+阿霉素5 mg·kg^-1组(Sham+DOX)、CCI模型+阿霉素5 mg·kg^-1组(Model+DOX)。造模成功后,各组采用尾静脉注射的方式给药,Sham组和Model组给予等量生理盐水,检测各组大鼠机械痛阈值和热痛阈值。在行为学检测结束后,即手术后d 15取大鼠右侧L4-5DRG,观察DRG细胞形态、超微结构及DOX的分布情况,采用Western blot法测定DRG组织中Bax、Bcl-2、PKCɑ、PKCδ及PKCε的蛋白表达。结果静脉注射DOX可在DRG组织检测到其自发荧光表达。与Sham组相比,Sham+DOX组痛阈值在整个观察期未见差别,而Model组在术后d 7痛阈值明显降低。与Model组相比,Model+DOX组的痛阈值在给药后明显回升,并表现出DRG细胞明显损伤,Bax/Bcl-2升高以及PKCδ、PKCε的蛋白表达量降低等现象。结论 DOX静脉注射可以到达并蓄积于DRG组织,明显减轻CCI大鼠的疼痛反应,这一作用与其降低PKCδ和PKCε的蛋白表达,诱导DRG的凋亡有关。     

鞘内注射米诺四环素对慢性坐骨神经结扎大鼠机械痛敏和热痛敏的影响

目的观察鞘内注射小胶质细胞抑制剂米诺四环素对慢性坐骨神经结扎大鼠机械痛敏和热痛敏的影响。方法所有大鼠术前8d鞘内置管,用机械缩足反射阈值和热缩足潜伏期来分别评价大鼠机械痛敏和热痛敏。前给药组:生理盐水10μl或米诺四环素50μg,于坐骨神经结扎前1d开始持续到术后1d(每天2次)鞘内注射,机械缩足反射阈值和热缩足潜伏期分别于术前2d,术后1,3,5,7,14d测定;后给药组:坐骨神经结扎后7d,鞘内注射1次生理盐水10μl或米诺四环素50μg,其对机械缩足反射阈值和热缩足潜伏期的影响分别于给药后0.5、1、2、4、8h测定。结果CCI大鼠从术后1d形成稳定的热痛敏和机械痛敏,前鞘内注射米诺四环素明显增加CCI大鼠MWT和TWL(P<0.05,P<0.01),相反,后鞘内注射米诺四环素对CCI大鼠MWT和TWL无明显影响。结论前鞘内注射米诺四环素明显抑制CCI大鼠机械痛敏和热痛敏,提示小胶质细胞的活化参与慢性坐骨神经结扎引发神经病理痛的形成。     

Individual differences in the sensitivity of cold allodynia to phentolamine in neuropathic rats

In neuropathic rats sensitive to phentolamine (alpha-adrenoreceptor antagonist, 2 mg/kg, i.p.), prazosin (alpha1-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) significantly attenuated cold allodynia whereas yohimbine (alpha2-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) had no significant effect. In neuropathic rats insensitive to phentolamine, yohimbine significantly exacerbated cold allodynia whereas prazosin had no significant effect. These results suggest that the individual differences in the sensitivity of cold allodynia to phentolamine may be due to the difference in the alpha-adrenoreceptor subtype predominantly involved in cold allodynia.     

肉毒毒素A对慢性坐骨神经结扎大鼠机械痛敏和热痛敏的影响

目的探讨肉毒毒素A(botulinum toxin type A,BoNT-A)后处理对神经病理性疼痛大鼠疼痛行为学的影响。方法建立SD大鼠右侧慢性坐骨神经结扎模型(chronic con-striction injury of sciatic nerve,CCI)。CCI术后d3始,CCI同侧肢体足底注射BoNT-A7.5、15、30U·kg-1或等容积生理盐水,或对侧肢体足底注射BoNT-A15或30U·kg-1。分别于术前、术后1、3、5、7、14d,测定大鼠的机械缩足反射阈值(MWT)和热缩足潜伏期(TWL)。结果CCI手术同侧足底皮下注射BoNT-A可以增加大鼠的MWT和TWL,对侧应用BoNT-A对MWT和TWL无影响。结论BoNT-A可以通过局部作用减轻CCI手术同侧肢体的机械痛敏和热痛敏。     

Characterization of primary sensory neurons mediating static and dynamic allodynia in rat chronic constriction injury model

Mechanical allodynia, such as static and dynamic allodynia, is a prominent feature of neuropathic pain syndromes. The aim of this study is to characterize primary sensory neurons mediating the mechanical allodynia in a rat chronic constriction injury (CCI) model with a combination of pharmacological and histological investigations. N-(4-Tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carbox-amide (BCTC), a selective and competitive antagonist of the vanilloid receptor 1 (TRPV1), and resiniferatoxin, which causes desensitization of TRPV1-expressing fibres, suppressed static allodynia but not dynamic allodynia in CCI rats. Immunohistochemical studies of TRPV1 and NF200, an A-fibre marker 200 kDa neurofilament, in dorsal root ganglion neurons demonstrated that each 48% of the positive-stained neurons were immunoreactive only for TRPV1 or NF200. The other 4% of stained neurons were double-positive for TRPV1 and NF200. Of the TRPV1positive neurons, more than 99% were small-(diameter <25 microm) and medium-(25-45 microm) sized. In contrast, 97% of NF200 single-labelled neurons were medium-and large-(>45 microm) sized. These findings suggest that two types of mechanical allodynia are transmitted by different primary sensory neurons: static allodynia is mediated by TRPV1 positive small-and medium-sized neurons and dynamic allodynia might be signalled by TRPV1-negative medium- and large-sized neurons.     

Ethosuximide reduces allodynia and hyperalgesia and potentiates morphine effects in the chronic constriction injury model of neuropathic pain

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system and treatment of neuropathic pain remains a challenge. The purpose of the present study was to examine the effect of ethosuximide, an anti-epileptic and relatively selective T-type calcium blocker and morphine, a prototypical opioid in the behavioral responses following the chronic constriction injury (CCI) model of neuropathic pain. Experiments were performed on eight groups (n=8) of male Sprague-Dawley rats (230-280 g). The animals were injected with saline, ethosuximide (100, 200, 300 mg/kg), morphine (4 mg/kg), and a combination of morphine (4 mg/kg) plus ethosuximide (100mg/kg, i.p.). The cold-and mechano-allodynia and thermal hyperalgesia were measured prior to surgery (the day 0) and 3, 5, 7, 14 and 21 days post surgery. Ethosuximide and morphine significantly decreased cold and mechano allodynia and thermal hyperalgesia. However, the co-administration of both drugs seems to be more effective than the ethosuximide or morphine alone on cold and mechano allodynia and thermal hyperalgesia .Our results suggest that ethosuximide block tactile and thermal hypersensitivity after the CCI model, also, ethosuximide potentiates the analgesic effects of morphine in neuropathic pain conditions and behavioral responses.     

细胞因子参与EPO预防神经病理性疼痛的机制探讨

目的 探讨预防性给予重组人红细胞生成素(rhEPO)对神经病理性疼痛大鼠模型机械、热痛觉高敏的影响及可能的机制.方法 雄性SD大鼠30只随机均分成三组.A、B组切断L5脊神经建立大鼠神经病理性疼痛模型;C组为假手术对照.术前1d,A组腹腔注射rhEPO 5000 U/kg,连续7d;B组腹腔注射生理盐水作为模型对照.采用von Frey仪测定各组0、3和7d机械缩足反射阈值;术后第7天用ELISA法测定大鼠L5脊髓组织TNF-α、IL-1β、IL-6和IL-10表达.结果 与C组相比,A、B组大鼠L5脊神经损伤术后,术侧均出现明显的机械痛阈下降(P＜0.01);但A组大鼠的机械痛高敏行为较B组明显缓解(P＜0.01).与C组比较,大鼠脊髓TNF-α、IL-1β、IL-6和IL-10表达明显增高(P＜0.01);与B组比较,A组脊髓组织IL-6水平明显降低,而IL-10水平明显升高(P＜0.01).结论 rhEPO能预防模型大鼠神经病理性疼痛的发生,其效应与减少促炎细胞因子和增加抗炎细胞因子释放有关.     

Changes of sleep patterns in rats with chronic constriction injury under aversive conditions

In the present study, we investigated the changes of sleep parameters in rats with chronic constriction injury (CCI) under aversive conditions. The electroencephalogram (EEG) in the frontal cortex of CCI rats and electromyogram (EMG) were measured over 6 h by placing rats on sandpaper as an aversive condition, to compare with rats placed on sawdust. Six days after CCI surgery, the rats exhibited significant mechanical allodynia, and also had neuropathic pain. When rats were placed on sawdust, no significant difference was observed between the CCI group and sham-operated control group in sleep latency, total waking time, total non-REM sleep time and total REM sleep time. On the other hand, when CCI rats were placed on sandpaper, a significant increase was observed in sleep latency and total waking time compared with the sham group; however, no significant difference was observed in the total non-REM sleep time and total REM sleep time between these two groups. These results indicate that an important factor of sleep disturbance in CCI rats is not only damage to the nerves but also being under aversive conditions. In addition, it was found that CCI rats placed on sandpaper as an aversive condition can serve as a new sleep disturbance model.     

Exploring the potential of telmisartan in chronic constriction injury-induced neuropathic pain in rats

The present study was designed to investigate the potential of telmisartan, an angiotensin AT(1) receptor, in chronic constriction injury-induced neuropathic pain in rats. Four loose ligatures were placed around the sciatic nerve to induce chronic constriction injury and neuropathic pain. Acetone drop, pin-prick, hot plate and paint brush tests were performed to assess cold allodynia; mechanical and heat hyperalgesia; and dynamic mechanical allodynia, respectively along with assessment of spontaneous pain and postural index in terms of foot deformity. The levels of TNF-α were measured in the sciatic nerve as an index of inflammation. Chronic constriction injury was associated with development of cold allodynia; mechanical and heat hyperalgesia; dynamic mechanical allodynia; and spontaneous pain and foot deformity along with rise in the levels of TNF-α. Telmisartan (1, 2, 5 mg/kg, p.o.) was administered for 14 days in chronic constriction injury subjected rats. Administration of telmisartan (2, 5 mg/kg) significantly attenuated chronic constriction injury-induced pain related behavior, foot deformity and rise in TNF-α level. It may be concluded that telmisartan has a potential in attenuating neuropathic pain behavior in chronic constriction injury model which may possibly be attributed to its anti-inflammatory properties.     

Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion

Rationale

Neuropathic pain is associated with significant co-morbidities, including depression, which impact considerably on the overall patient experience. Pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. Neuropathic pain is characterized by hyperexcitability within nociceptive pathways and remains difficult to treat with standard analgesics.

Objectives

The present study determined the effect of bis selenide and conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on neuropathic pain using mechanical allodynic and on depressive-like behavior.

Methods

Male mice were subjected to chronic constriction injury (CCI) or sham surgery and were assessed on day 14 after operation. Mice received oral treatment with bis selenide (1–5 mg/kg), fluoxetine, amitriptyline, or bupropion (10–30 mg/kg). The response frequency to mechanical allodynia in mice was measured with von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for depression-like behavior.

Results

The CCI procedure produced mechanical allodynia and increased depressive-like behavior in the FST. All of the drugs produced antiallodynic effects in CCI mice and produced antidepressant effects in control mice without altering locomotor activity. In CCI animals, however, only the amitriptyline and bis selenide treatments significantly reduced immobility in the FST.

Conclusion

These data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide and amitriptyline but not by the conventional antidepressants fluoxetine and buproprion. Bis selenide was more potent than the other drugs tested for antidepressant-like and antiallodynic effects in mice.     

Involvement of the multidrug resistance transporters in cisplatin-induced neuropathy in rats. Comparison with the chronic constriction injury model and monoarthritic rats

It has recently been suggested that P-glycoprotein is involved in the genesis and the treatment of the neurotoxic adverse events of anticancer drugs, including vincristine. A lower activity of P-glycoprotein in the peripheral nervous system (PNS) than in the central nervous system could contribute to the neurotoxicity of vincristine. Vincristine treatment is responsible for the induction of multidrug resistance (MDR) gene expression and transporter activity, with deleterious consequences, including a potential decrease in the efficiency of opioid analgesics, antidepressants or antiepileptics. Concerning cisplatin, which is also a strong neurotoxic drug but only an multidrug resistance protein 2 (MRP2) substrate, the same assumption could be suggested for MRP2 nervous function. The aim of this study was to assess MDR gene and protein activity in a rat model of cisplatin-induced neuropathy compared with different peripheral nerve injury models, i.e. mononeuropathy and inflammatory pain (monoarthritis). First, in cisplatin-induced neuropathy, this study demonstrated low MRP2 gene expression in dorsal root ganglia compared with the brain and spinal cord, which could contribute to the strong neurotoxicity of cisplatin in the PNS and particularly the dorsal root ganglia. Thus, gene expression increased in cisplatin-induced neuropathy but decreased in mononeuropathy and remained unchanged in monoarthritis models. Transporter activity of nervous tissues increased in the cisplatin-induced neuropathy, mononeuropathy and monoarthritis to different intensities (3.7-, 1.8- and 1.8-fold, respectively). The development of a MDR in the cisplatin-induced neuropathy is a striking difference with mononeuropathy and monoarthritis models, and characterizes the neuropathies induced by this anticancer drug.     

乳铁蛋白在大鼠坐骨神经慢性束缚损伤模型产生镇痛作用

目的:研究乳铁蛋白在大鼠坐骨神经慢性束缚损伤模型的镇痛作用。方法:30只成年SD大鼠被制作为坐骨神经慢性束缚损伤模型,用辐射热刺激法诱发鼠后腿回缩试验测定痛阈,实验动物分为5组,分别腹腔注射生理盐水及乳铁蛋白30mg/kg、100mg/kg、300mg/kg、1000mg/kg。药物效应以最大可能效应百分数(MPE%)表示。以t检验法分析乳铁蛋白各剂量组与对照组之间的差异。结果:腹腔注射乳铁蛋白剂量依赖性地延长大鼠后腿回缩潜伏期;乳铁蛋白的峰值作用时间在用药后60分钟;乳铁蛋白各剂量组的最大可能效应百分数与生理盐水组相比差异有显著性。结论:腹腔注射乳铁蛋白在大鼠坐骨神经慢性束缚损伤模型产生剂量依赖性镇痛作用。     

非诺贝特对慢性心力衰竭大鼠心室重构的影响

目的研究非诺贝特对慢性心力衰竭大鼠心室重构的影响。方法 68只8周龄健康♂Wistar大鼠随机分为假手术组(Sh组,18只)和模型组(M组,50只),模型制备采用腹主动脉缩窄术,8周后将成功存活的38只模型组大鼠随机分为非诺贝特组(F组,18只)和对照组(C组,20只),分别给予非诺贝特150 mg.kg-1或生理盐水灌胃,每天1次,共10周。结果①干预前后,与Sh组比较,C组及F组LVEF、FS%、±dp/dtmax均降低(P<0.05),LVEDd、LVEDs、LVSP、LVEDP均升高(P<0.05);C组与F组间差异无统计学意义(P>0.05)。②干预后,C组、F组心肌LVW/BW、CVF指标较Sh组增高(P<0.05);F组LVW/BW较C组增高、CVF指标较C组明显降低(P<0.05)。③干预后,与Sh组比较,C组和F组心肌ET-1 mRNA明显增高(P<0.05);与C组比较,F组明显降低(P<0.05)。④干预后,与Sh组比较,F组和C组心肌eNOS蛋白水平明显降低(P<0.05);与C组比较,F组明显升高(P<0.05)。结论非诺贝特下调慢性心力衰竭大鼠心肌ET-1基因表达,上调eNOS的表达,抑制心肌间质纤维化,改善心室重构;但对心脏功能无影响。     

Titration procedure with rats using a nose poke response and tail shock

An operant titration procedure that provides relatively stable within-session shock thresholds (0.15–0.25 mA) within a week of training is described. Rats are placed into Plexiglas restraint tubes having a hole at one end through which the animal can poke its nose to break a photobeam; when the photobeam is broken, a response is counted. The tail of the animal is firmly held by a Plexiglas plug and an electrode connected to a programmable titration shocker is attached to the tail. Conditioned nose poke responses are made after about 15 min during the first 30 min session. The titration procedure was found to be sensitive to the analgesic effect of morphine. Significant increases in the median shock level tolerated was observed after 3 mg/kg, while response rate was not altered. Dose-related increases in threshold after 6 and 9 mg/kg of morphine were associated with decreases in the rate of nose poking. The technique offers several advantages in the study of chemical induced alterations in pain or reactivity, including rapidity of initial training, relatively short time to establish median shock thresholds, minimum involvement of motor components in the response, and sensitivity to a psychopharmacological tool.     

Effects of chronic ethanol consumption on aortic constriction in male and female rats

This study was designed to determine if gender influences the effects of chronic ethanol intake on vasoconstrictive responsiveness. Ethanol-preferring rats were allowed ad libitum access to tap water or tap water containing 20% or 30% ethanol for 16 weeks. All of the ethanol groups consumed more daily calories than their respective controls, and female rats consumed more ethanol calories per unit body mass than their male counterparts. Following treatment, endothelium-intact and endothelium-denuded thoracic aortic rings were used to examine the contractile response to phenylephrine. Ethanol consumption did not alter vasoconstriction in endothelium-intact aortae from either gender. In contrast, males, but not females, demonstrated an ethanol-associated increase in the maximum response to phenylephrine in endothelium-denuded preparations. Aortae from male rats that consumed 20% and 30% ethanol showed an increased contractility of 37% and 85%, respectively. These data indicate that gender influences the vasoconstrictive effects elicited by chronic ethanol consumption and suggest that males may be more susceptible to the associated hypertension.     

Acetaminophen-induced hepatotoxicity in rats is correlated with the accumulation of bile acids: an underlying mechanism

In the present study, we aimed to investigate the underlying mechanism of acetaminophen (APAP)-induced hepatotoxicityby measuring the expression levels of liver transporters and concentrations of bile acids (BAs) in rat plasma and liver. SD rats (42)were randomly assigned into six groups, including 6-h control group, APAP 6-h group, 12-h control group, APAP 12-h group, 24-h control group and APAP 24-h group. The estimation study of BAs in plasma and liver was performed on LC-MS/MS.The levels of bile salt export pump (Bsep), multidrug resistant protein 2 (Mrp2), multidrug resistant protein 4 (Mrp4), Na⁺/taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide 2 (Oatp2) in the liver were analyzed by Western blotting analysis. Compared with the corresponding control groups, no difference was found in the BA levels and the expressions of BA transporters in the plasma and liver after 6 h of APAP administration. While BA levels were significantly decreased in the plasma and increased in the liver after 12 h of APAP administration (P<0.05); and the expressions of Bsep and Mrp2 were significantly reduced (P<0.05). After 24 h of APAP administration, BA levels were both greatly increased in the plasma and liver (P<0.05); and the expressions of Mrp4 and Oatp2 were significantly decreased (P<0.05). In response to over-dose APAP, Bsep, Mrp2, Mrp4 and Oatp2 levels were reduced at different time points, causing the accumulation of BAs, and such accumulation may ultimately lead to the severe liver injury, which could be an underlying mechanism of the APAP-induced hepatotoxicity.     

甘草酸二铵抗大鼠溃疡性结肠炎作用及相关机制研究

目的:研究甘草酸二铵(DG)对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎的作用及可能作用途径。方法:以柳氮磺吡啶(SASP,225 mg.kg-1)为阳性对照,研究甘草酸二铵结肠给药(2,10,50 mg.kg-1,qd,共给药7 d)对TNBS性溃疡性结肠炎大鼠的结肠单位长度重量、结肠黏膜损伤评分、髓过氧化物酶(MPO)、结肠组织丙二醛(MDA)和超氧化物歧化酶(SOD)以及血清白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量的影响;由HE染色、扫描和透射电镜观察结肠组织病理学变化;由免疫组化观察结肠组织环氧酶-2(COX-2)和细胞间黏附分子-1(ICAM-Ⅰ)表达的变化。结果:模型动物结肠组织发生明显病理学变化,伴有充血、溃疡以及大量的炎性细胞浸润,DG组均不同程度改善结肠组织病理学变化,降低单位长度结肠重量,并呈剂量依赖关系。与正常组比较,模型组大鼠结肠组织中MPO活性和MDA含量显著升高,SOD活性明显下降;DG能显著逆转模型组MPO,MDA和SOD的变化。与模型组比较,DG组结肠组织COX-2和ICAM-Ⅰ表达下调,血清中IL-1β和TNF-α表达量也有不同程度下降。结论:甘草酸二铵能有效改善溃疡性结肠炎大鼠的结肠炎症反应,其作用机制与抗氧化、降低促炎性细胞因子水平等有关。     

坐骨神经慢性压迫损伤性疼痛与脊髓背角P物质关系研究

目的观察大鼠坐骨神经慢性压迫性损伤（CCI）后脊髓背角P物质表达的变化,探讨P物质在疼痛发生机制中的作用。方法SD雄性大鼠60只,随机分为：A组：CCI组（30只）;B组：对照组（30只）。术前及术后3、7、14、28 d分别测定大鼠热痛阈值、机械痛阈值和行为学评分。术后3、7、14、28d每组取4只,麻醉后用4%多聚甲醛灌注固定,取L4-6段脊髓,以备免疫组化,测定SP的变化。结果所有CCI动物从术后第3天起,出现明显的疼痛行为学改变和热痛阈值、机械痛阈值的降低,与对照组比较差异有统计学意义（P〈0.05或P〈0.01）。免疫组织化学结果表明,A组术后术侧明显高于B组（P〈0.05或P〈0.01）;A组术侧明显高于健侧（P〈0.05或P〈0.01）;而B组仅在第4天术侧高于健侧（P〈0.05）。结论慢性坐骨神经损伤后,脊髓背角SP的表达增加,而且表达增加与CCI大鼠的痛觉过敏、行为变化在时相上基本一致,说明CCI大鼠痛觉过敏与脊髓背角SP的表达增加有关。     

κ阿片受体在抗缺血/再灌注大鼠心律失常中的作用机制

目的研究κ阿片受体在抗缺血/再灌注性心律失常中的作用机制,并初步探讨κ阿片受体选择性激动剂U50488H(U50)对大鼠血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET)和一氧化氮(NO)的调控作用。方法实验大鼠随机分为7组,即对照组(Control),缺血再灌注组(I/R),U50+I/R组,PTX组(pertussis toxin,百日咳毒素,G i/o蛋白抑制剂),G lib组(glibenc lam ide,KATP通道阻断剂),Che组(chel-erythrine,PKC选择性抑制剂)和Gen组(gen iste in,酪氨酸激酶TK抑制剂),观察心律失常发生情况并计算心律失常评分;检测血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET)和一氧化氮(NO)水平。结果①与I/R组相比,U50488H+I/R组大鼠心律失常评分明显下降,该作用可被选择性κ阿片受体阻断剂nor-BNI阻断。②分别提前给予PTX,glibenc lam ide和chelerythrine后,U50488H的抗心律失常作用可被明显减弱或阻断;③提前给予gen iste in对U50488H的抗心律失常作用无明显影响。④与正常大鼠血浆AngⅡ、ET和NO含量比较,I/R组血浆AngⅡ和ET含量明显增加,NO含量明显降低;给予U50488H处理后,U50+I/R组大鼠血浆AngⅡ和ET含量比I/R组降低,而NO含量则明显升高。结论①κ阿片受体介导了抗缺血/再灌注性心律失常的作用,该作用的信号转导途径可能涉及G i/o、PKC和KATP等通道。②激活κ阿片受体还可能通过下调大鼠血浆AngⅡ和ET或上调NO等因子的水平来发挥抗心律失常作用。