巴氏蘑菇多糖对糖尿病小鼠脂代谢紊乱的干预作用

选择健康雄性昆明小鼠随机分组,建立糖尿病小鼠模型后分别灌胃不同剂量的巴氏蘑菇(Agaricus blazei)多糖(低、中和高剂量组分别灌胃50、100和200mg/kg/d),阳性对照组灌胃200mg/kg/d阿卡波糖,正常对照和模型组灌胃生理盐水,7周后考察巴氏蘑菇多糖对糖尿病小鼠脂代谢的影响。结果表明:与糖尿病模型组相比,多糖各剂量组和阳性对照组空腹血糖值和血清总胆固醇含量均显著下降;多糖中、高剂量组和阳性对照组的血清甘油三酯含量也显著下降;与模型组相比,附睾脂肪中阳性对照组的glut4、pi3k、akt1和akt2mRNA的表达量均显著升高,多糖组中glut4(低、中和高剂量组)、akt1(低、中和高剂量组)、akt2(中和高剂量组)和pi3k(高剂量组)mRNA的表达量显著升高。     

掌状玫耳粗多糖对环磷酰胺所致小鼠免疫低下的影响

采用掌状玫耳（Rhodotus palmatus）粗多糖（低、高剂量分别为100、200 mg·kg-1）腹腔注射环磷酰胺所致免疫低下小鼠，测定脾脏、胸腺指数，血清中TNF-α、IL-1β、IL-6、溶血素含量，耳肿胀度，血液中白细胞、红细胞、血红蛋白、血小板含量，血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）活性，血清中尿素氮（BUN）、肌酸酐（CRE）含量，并测定脾脏组织NF-κB通路相关蛋白表达量，研究掌状玫耳粗多糖对免疫低下小鼠免疫功能的影响。结果表明：与模型组相比，掌状玫耳粗多糖高、低剂量组小鼠胸腺、脾脏指数均显著增加；高剂量组TNF-α、IL-1β和IL-6含量显著增加；高、低剂量组小鼠耳肿胀度均显著增加；高剂量组小鼠血清溶血素含量显著增加；高剂量组小鼠血液中白细胞、红细胞、血红蛋白含量显著增加，高、低剂量组小鼠血液中血小板含量均显著增加；高剂量组小鼠血清中ALT活性显著降低，高、低剂量组小鼠血清中AST活性和CRE、BUN含量均显著降低；高、低剂量组TLR-4、IKKα、NF-κBp50表达量均显著升高，IκB-α表达量显著降低；高剂量组NF-κB p65表达量极显著升...     

广叶绣球菌多糖对高脂小鼠肝脏氧化应激调节作用

通过小鼠肝脏指数测定、肝脏的组织形态HE染色观察、肝脏脂质代谢和抗氧化指标测定，并采用实时荧光定量PCR技术检测肝脏抗氧化应激反应及炎症相关基因表达量，研究广叶绣球菌(Sparassis latifolia)多糖(SLP，低、中、高剂量分别为100、200、400 mg·kg^-1)对高脂小鼠肝脏氧化应激的调节作用。结果表明：与模型组相比，SLP中、高剂量组的肝脏指数显著降低；高剂量组肝脏的TC、TG含量均显著降低，低、中、高剂量组的LDL-C含量极显著降低；中、高剂量组的MDA含量显著降低，高剂量组的SOD、GSH-Px活性和GSH含量均显著升高；低、中、高剂量组的HO-1、GST表达量均显著升高，高剂量组的NQO1表达量显著升高，中、高剂量组的γ-GCL表达量显著升高；高剂量组的CRP、IL-6、TNF-α表达量均极显著降低，中、高剂量组的VCAM-1表达量极显著降低，低、中、高剂量组的ICAM-1表达量极显著降低，表明广叶绣球菌多糖可通过提高肝脏的抗氧化能力，调节炎症相关基因表达，改善高脂饮食导致的小鼠肝损伤。研究结果可为广叶绣球菌多糖开发提供参考。     

广叶绣球菌多糖对免疫低下小鼠大脑皮质损伤的调节作用

通过腹腔注射环磷酰胺溶液(80 mg·kg-1)构建免疫低下小鼠模型,灌胃广叶绣球菌(Sparassis latifolia)多糖(SCPs)(低、中、高剂量分别为100、200、400 mg· kg-1),通过制备苏木精-伊红(HE)染色切片观察小鼠大脑皮质形态变化;测定小鼠大脑皮质中丙二醛(malondialdeh...     

刺芹侧耳多肽对染铅大鼠脑海马组织形态及海马组织中camk2a、erk2和homer1基因mRNA表达量的影响

为研究刺芹侧耳(Pleurotus eryngii)多肽对染铅大鼠脑组织损伤的影响,以雄性SD大鼠为研究对象,随机分为正常对照组(基础饲料,蒸馏水)、染铅模型组(基础饲料,0.2%醋酸铅水溶液)和多肽组(添加2%多肽的基础饲料,0.2%醋酸铅水溶液),饲养60d后,观察大鼠脑部海马组织形态变化,测定海马组织中铅含量、camk2a、erk2和homer1mRNA的表达量。结果表明:铅会导致海马组织的细胞数量减少、细胞层变薄、细胞间隙增大、camk2a、erk2和homer1mRNA表达量极显著降低;与染铅模型组相比,多肽组海马组织的铅含量显著降低、细胞数目增多、细胞核变大、细胞间隙缩小,同时海马组织中NMDAR和mGluR5信号通路相关基因camk2a、erk2和homer1mRNA的表达量显著或极显著升高,表明刺芹侧耳多肽可减轻铅对大鼠海马组织的损伤。     

蛹虫草多糖对小鼠抗疲劳作用的研究

采用雄性ICR小鼠随机分组,分别灌胃蒸馏水、不同剂量的蛹虫草(Cordyceps militaris)多糖(低、中、高剂量组分别每天灌胃75、150、450mg/kg BW),40d后建立疲劳模型,比较力竭游泳时间、肝肌糖原水平、乳酸含量和机体相关的乳酸脱氢酶和超氧化物歧化酶活力。结果表明:高剂量蛹虫草多糖能够显著延长小鼠力竭游泳时间,中高剂量多糖显著提高小鼠肝肌糖原水平,有效的遏制运动后小鼠乳酸生成量,而低剂量多糖显著增加运动后小鼠乳酸脱氢酶活力,3个剂量的多糖均能提高运动后小鼠血清中超氧化物歧化酶的活力。     

白灵菇多糖对CCI4损伤的小鼠心脏抗氧化作用研究

目的:探讨白灵菇多糖对CCI4损伤小鼠心脏抗氧化作用.方法:将成年小鼠随机分为正常对照组、模型对照组、低剂量组、中剂量组和高剂量组(低、中、高剂量给予的白灵菇多糖每天分别为100、200、500 mg/kg共5组,连续灌胃30d后,模型对照组及3个试验组以5 mg/kg·d·wt的量,灌以用色拉油配制的1%CCL溶液,正常对照组灌以等体积的色拉油.24h后将各组动物处死,测定心脏器官的总SOD、Mn-SOD、MDA、GSH-Px几个主要抗氧化指标.结果:与模型对照组相比,给予中、高剂量的白灵菇多糖,可显著提高受损小鼠心脏的总SOD、Mn-SOD及GSH-Px几个主要抗氧化指标.结果:与模型对照组相比,给予中、高剂量的白灵菇多糖,可显著提高受损小鼠心脏的总SOD、Mn-SOD及GSH-Px的活性,降低MDA的含量.结论:对于CCI4损伤的小鼠心脏,白灵菇多糖具有较好的抗氧化作用.     

金针菇多糖改善小鼠学习记忆功能

研究金针菇多糖对正常小鼠学习记忆的影响。利用三等分辐射式迷宫箱训练小鼠,检测每实验日正确反应率、达标小鼠的比率及达标所需训练次数,训练结束后取脑,用紫外分光光度计检测各项指标的OD值,测得超氧化物歧化酶（SOD）和丙二醛（MDA）含量。结果显示低剂量金针菇多糖可显著提高小鼠的达标率,显著降低小鼠达标的训练次数,金针菇多糖对SOD含量水平均有显著的提高作用（p〈0.05）,低剂量的金针菇多糖明显提高大脑海马组织中蛋白质的含量（p〈0.05）并能显著降低MDA含量（p〈0.05）。这表明金针菇多糖对小鼠的学习记忆有一定的促进作用,并能显著提高大脑海马组织中的蛋白质含量,提高SOD活力,降低MDA含量,表现出明显的抗氧化作用。     

长柄侧耳人参菌质多糖预防小鼠高血脂的研究

目的:研究长柄侧耳菌质多糖以及培养基中加人参药渣的菌质混合多糖对小鼠高脂血症的预防作用。方法:将健康昆明小鼠随机分为5组,分别为空白组、模型组、阳性对照组、长柄侧耳菌质多糖组、长柄侧耳人参菌质多糖组,除空白组外均喂高脂饲料。各组小鼠每天灌胃给药一次,连续灌胃45d后,小鼠断头取血,分离血清,测血清中的总胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)和低密度脂蛋白胆固醇(LDLC)含量。结果:长柄侧耳菌质多糖和长柄侧耳人参菌质多糖都能显著降低高脂小鼠CHO、TG、LDLC含量,有显著性升高HDLC含量的作用。结论:长柄侧耳菌质多糖、长柄侧耳人参菌质多糖均能有效调节机体脂质代谢,对小鼠高脂血症具有预防作用。     

桑黄菌丝体对小鼠肉瘤S_(180)的抑制作用

建立荷瘤(S180)小鼠模型,用桑黄(Phellinus igniarius)菌丝体灌胃(低、中和高剂量组分别为0.25、0.5和1.0g/kg/d)至模型组肿瘤直径达1cm停止给药,测定抑瘤率和各脏器指数。结果表明:阳性对照组(顺铂3mg/kg/d)显著抑制小鼠体重的增加,而桑黄菌丝体3个剂量组对小鼠体重的增加没有显著的抑制作用;低、中和高3个剂量组抑瘤率分别为18.3%、29.5%和40.7%。桑黄菌丝体对脾脏指数与胸腺指数的影响小于阳性对照药物顺铂。     

Hyperbaric oxygen therapy activates CREB/BDNF signaling pathway to reduce synaptic damage in hippocampal neurons of Alzheimer disease mice

AIM To investigate the effect of hyperbaric oxygen (HBO) on synaptic damage of hippocampal neurons in APP/PS1 transgenic (TG) mice and its possible mechanism. METHODS The 6-month-old male APP/PS1 TG mice were randomly divided into TG group, HBO group and cAMP response element binding protein (CREB) inhibitor H89 group, with 10 mice in each group. Ten male wild-type (WT) C57BL/6 mice of the same age were used as negative control group (WT group). The mice in HBO and H89 groups were treated with HBO for 6 cycles, while the mice in WT group and TG group were not treated. The learning and memory abilities were observed by Morris water maze. The nesting ability of the mice was detected by nesting test. The Nissl bodies in hippocampal neurons were observed by Nissl staining. The mRNA expression of CREB and brain-derived neurotrophic factor (BDNF) in hippocampus was detected by real-time PCR. The protein levels of synapsin (SYN), postsynaptic density protein 95 (PSD95), growth-associated protein 43 (GAP43), CREB, phosphorylated CREB (p-CREB) and BDNF in the hippocampus were determined by Western blot. RESULTS Compared with WT group, the learning and memory abilities of the mice in TG group were signilficantly reduced (P<0.05). In addition, the nesting score, the number of Nissl bodies in the hippocampal neurons, the mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P<0.05). Compared with TG group, the learning and memory abilities of the mice in HBO group were improved (P<0.05). Meanwhile, the nesting scores of the mice were significantly increased (P<0.05), the neurons in the hippocampus were arranged neatly, and the number of Nissl bodies, the relative mRNA expression of CREB and BDNF,and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also increased significantly (P<0.05). Compared with HBO group, the mice in H89 group had poor learning and memory abilities, lowered nesting scores and decreased number of Nissl bodies. Futhermore, the relative mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P<0.05). CONCLUSION HBO improves the learning and memory abilities of APP/PS1 TG mice, and its mechanism may be related to activating the CREB/BDNF signaling pathway to reduce synaptic damage of hippocampal neurons in mice.     

Phosphodiesterase 4 inhibitor rolipram prevents chronic alcoholism and withdrawal-induced depression-like behaviors in mice

AIM: To investigate the effect of phosphodiesterase 4 (PDE4) inhibitor rolipram on the levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus and the prefrontal cortex (PFC) of alcoholism model mice.METHODS: The mice (n=60) were randomly divided into control group, control+rolipram group, alcoholism model group, and alcohol+rolipram (0.1, 0.5 and 1 mg/kg) groups. The mice were given alcohol preference test on days 6, 13, 20 and 27. After the test, the mice received withdrawal of alcohol for 1 d. On day 28, the mice were given behavior test of depression, and after the test, the mice were sacrificed. The cAMP levels in the hippocampus and PFC were detected by ELISA, and the protein levels of PKA, CREB, p-CREB and BDNF were detected by Western blot.RESULTS: The mice showed an obvious drinking phenomenon (P<0.01), and the immobility time of forced swimming test and tail suspension test was significantly increased (P<0.01), with increasing drinking days and withdrawal times. However, chronic treatment with rolipram for 28 d reversed this phenomenon. Moreover, the cAMP levels in the hippocampus and PFC were significantly decreased after 28 d alcohol treatment (P<0.01), and pretreatment with rolipram (1 mg/kg) obviously reversed this decrease (P<0.01). Parallel to these changes of cAMP, the protein levels of PKA, p-CREB and BDNF were also decreased in the hippocampus and PFC (P<0.01), and 28 d rolipram administration inhibited the decreased cAMP, PKA, p-CREB and BDNF levels in the hippocampus. Moreover, 28 d rolipram administration also reversed decreased cAMP, PKA and p-CREB in the PFC.CONCLUSION: Rolipram treatment protects against alcohol-induced depression-like behaviors, and also reduces alcohol drinking. These effects may be related to PDE4-cAMP-PKA-CREB-BDNF pathway.     

Change of depression-like behavior in chronic alcoholism and withdrawal model,and co-mechanism of depression and chronic alcoholism in mice

AIM: To investigate the behavior of depression in chronic alcoholism and withdrawal model of mice, and to explore the co-mechanism of alcoholism and depression. METHODS: A novel model of chronic alcoholism was constructed in this study. The animals were divided into normal control group, and alcohol 7 d, 14 d, 21 d and 28 d groups. The mice were given alcohol preference test on the 6th, 13th, 20th and 27th days. After the test, alcohol were withdrawn for 1 d, then the next day the mice were given behavior test of depression. After the test, the mice were sacrificed. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were detected by HPLC. The expression of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) was detected by Western blot. RESULTS: The mice showed an obvious drinking phenomenon, and the immobility time of forced swimming test and tail suspension test was significantly increased, with increasing drinking days and withdrawal times. 5-HT level in 7 d group mice only increased in frontal cortex (P < 0.05). However, compared with control group, 5-HT levels in hippocampus and cortex were decreased on the 21th and 28th days (P < 0.01). NE levels in 21 d and 28 d groups were decreased in hippocampus and frontal cortex (P < 0.05), and no significant change was observed in 7 d and 14 d groups. The protein levels of p-CREB and BDNF were significantly decreased in hippocampus and frontal cortex of 12 d and 28 d groups (P < 0.05), and no significant change was observed in 7 d group and 14 d group. CONCLUSION: The co-mechanism of alcoholism, withdrawal and depression is related to 5-HT. 5-HT-cAMP-CREB-BDNF signaling pathway may be a common mechanism for alcoholism and depression.     

Phosphodiesterase 4 inhibitor rolipram prevents depression- and anxiety-like behaviors in rats exposed to chronic restraint stress

AIM: To discuss the impact of phosphodiesterase 4 (PDE4) inhibitor rolipram on chronic restraint stress-induced depression- and anxiety-like behaviors in rats. METHODS: (1)Forty SD rats were randomly divided into 4 weight-matched groups: unstressed animals injected with vehicle of lithium chloride (LiCl) and rolipram, restraint-stressed animals injected daily with vehicle prior to stress, restraint stress plus 100 mg/kg LiCl group and restraint stress plus 1 mg/kg rolipram group. The open field test was conducted 24 h before the first stress and drug administration,and then the rats received drugs daily 1 h prior to restraint stress (6 h/d) for 25 d. Daily body weight recording, forced swimming test, elevated plus-maze and open field test were conducted to determine the changes of depression- and anxiety-like behaviors. The expression of phosphorylated cAMP response element-binding protein (p-CREB), brain-derived Reurotrophic factor (BDNF), p-Ser21-glycogen synthase kinase (GSK) 3α, p-Ser9-GSK3β, p-Tyr279-GSK3α, p-Tyr216-GSK3β, total GSK3α and total GSK3β was measured by Western blotting. (2)Thirty SD rats were randomly divided into 6 groups and the cannula was surgically placed above the CA1 region in the hippocampus. Seven days after the surgery, the restraint stress was conducted for 21 d after microinjection of protein kinase A (PKA) antagonist H89 and intraperitoneal injection of LiCl and rolipram everyday. The expression of PDE4D, PKA, p-CREB and p-Ser9-GSK3β was measured by Western blotting. RESULTS: (1)No difference of the locomotor activity among all groups before stress was observed. After repeated stress, the body weight,and the crossing, rearing and grooming in open field test were lower than those in control group, and LiCl and rolipram reversed these effects significantly. In addition, in comparison with control group, the immobility in forced swimming test was increased, the climbing in forced swimmming test and the open-arm exploration in elevated plus-maze were decreased and the expression of p-CREB, BDNF, p-Ser21-GSK3α and p-Ser9-GSK3β was down-regulated. Stress induced depression- and anxiety-like behaviors, and rolipram reversed these changes. The LiCl showed similar effects as rolipram except for the expression of p-CREB and BDNF. No significant difference of the expression of p-Tyr279-GSK3α, p-Tyr216-GSK3β, total GSK3α and total GSK3β among all groups was found. (2)The expression of PDE4D was increased, the expression of PKA, p-CREB and p-Ser9-GSK3β was decreased in the hippocampus induce by restraint stress. However, the effect of rolipram on the expression of PKA, p-CREB and p-Ser9-GSK3β was blocked by PKA inhibitor H89. CONCLUSION: Rolipram significantly reduces the depression- and anxiety-like behaviors, possibly through CREB/BDNF signaling and inhibitory serine-phosphorylation of GSK3-mediated signaling. Importantly, the CREB/BDNF signaling also plays a key role in the down-regulation of serine-phosphorylation of GSK3.     

Effects of dexmedetomidine on behaviors and expression of BDNF and mTOR in hippocampus of depressive rats

AIM: To investigate the effects of dexmedetomidine (DEX) on the behaviors and the expression of brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the hippocampus of depressive rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation group, model group, and DEX (2.5, 5 and 10 μg/kg) groups. The rats were randomly selected in each group (n=12). The rat depression model was established by chronic unpredictable mild stress and ovariectomy. The rats in DEX groups received daily DEX treatment via intraperitoneal injection for 21 d. The forced swimming immobility time (FSIT) and open-field test were used to evaluate the antidepressant effect of DEX. Escape latency and times of crossing the flat were evaluated by Morris water maze. The histological changes of hippocampal neurons were determined by Nissl staining. The mRNA levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by RT-qPCR. The protein expression of IL-1β, IL-6, TNF-α and BDNF, and the phosphorylation levels of protein kinase A (PKA), cAMP response element-binding protein (CREB), tropomyosin-related kinase B (TrkB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mTOR in hippocampus were evaluated by Western blot. RESULTS: Compared with model group, the FSIT was significantly reduced and the spontaneous activity was markedly increased in DEX groups. The damage of the hippocampal neurons was obviously attenuated, the escape latency was obviously decreased, and times of crossing the flat were markedly increased (P<0.05 or P<0.01). The levels of IL-1β, IL-6 and TNF-α were obviously decreased, and the protein levels of p-PKA, p-CREB, BDNF, p-TrkB and p-PI3K, p-Akt, p-mTOR in hippocampal tissues were obviously increased (P<0.05 or P<0.01). CONCLUSION: Dexmedetomidine improves the behaviors and the spatial learning and memory ability of depressive model rats, which may be related to its anti-inflammatory effects, as well as up-regulating the protein levels of BDNF and p-TrkB, and activating PI3K/Akt/mTOR signaling pathway in the hippocampus.     

Alterations in rat hippocampal norepinephrine and serotonin levels under physical exercise and psychological stress

AIM: This study is to determine changes of hippocampal norepinephrine (NE) and serotonin (5-HT) in long term physical exercise and chronic psychological stress, and to study the roles of the two monoamine transmitters in the effect of exercise counteracting stress-induced hippocampal damages in brain. METHODS: Levels of hippocampal NE and 5-HT in rats undergoing 4-week voluntary wheel running exercise (exercise group) or 3-week restraint stress (stress group) or 4-week exercise and 3-week stress (exercise-stress group) were detected by high-performance liquid chromatography using electrochemical detection. RESULTS: It is showed that levels of hippocampal NE and 5-HT increased significantly (P<0.01) in the exercised rats, and in the stressed rats,hippocampal 5-HT levels significantly decreased(P<0.05). Additionally, the NE levels maintained significant high (P<0.01) in exercise-stressed rats compared to the pure stressed ones. On the other hand, no obvious difference was observed in hippocampal 5-HT levels between stress group and exercise-stress group, which were all significant lower (P<0.05) than that in exercise group. CONCLUSION: It is suggested that both the NE and 5-HT may play important roles in mediating the exercise-induced positive effects and the 5-HT may play an important role in stress-induced negative effects on the hippocampus. Moreover, NE may take more action in the exercise attenuating stress-induced hippocampal damages. The hippocampal NE may be more susceptible to exercise, and the hippocampal 5-HT may be more susceptible to stress.     

Effects of clonidine on learning and memory and protein levels of ERK signal pathway-related proteins in rats with chronic cerebral ischemia

AIM:To investigate the regulatory effects and underlying molecule-mechanism of clonidine on learning and memory in rats with chronic cerebral ischemia. METHODS:Sprague-Dawley rats (n=45) were randomly divided into sham-operation group, cerebral ischemia model group and clonidine group, 15 rats in each group. The chronic cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2 h and reperfusion for 30 d. Clonidine was administrated by i.g. for 7 days in clonidine group. The ability of spatial reference memory of the rats with cerebral ischemia was tested by Morris water maze. The protein levels of extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), cAMP-response element binding protein (CREB) and phosphorylated CREB (p-CREB) were determined by immunohistochemistry and Western blot. RESULTS:The results of Morris water maze test showed that compared with the sham-operation group, the ability of spatial reference memory was obviously impaired in the cerebral ischemia model group. Compared with the cerebral ischemia model group, the ability of spatial reference memory in the clonidine group were improved. Compared with the sham-operation group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were increased in model group (P<0.01). Compared with the cerebral ischemia model group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were decreased in the clonidine group (P<0.01). CONCLUSION:Clonidine improves the learning and memory abilities of the rats with cerebral ischemia, and ERK1/2 and CREB are involved in this process.     

Analgesic effect of angiotensin angiotensin Ⅱ type 2 receptor antagonist EMA401 on neuropathic pain in rats and its mechanism

AIM: To explore whether angiotensin Ⅱ type 2 receptor antagonist EMA401 decreases neuropathic pain and the expression of growth-associated protein-43 (GAP-43), protein kinase C (PKC) and calmodulin (CaM) in dorsal root ganglia (DRG) during chronic constriction injury (CCI) in rats. METHODS: SD rats were used to establish CCI model and randomly divided into 4 groups. The rats in model group were given equal volume of normal saline by intragastric administration. The rats in low dose (LD) group were given 5 mg/kg EMA401 by intragastric administration. The rats in middle dose (MD) group were given 10 mg/kg EMA401 by intragastric administration. The rats high dose (HD) group were given 20 mg/kg EMA401 by intragastric administration. The rats in sham operation group received equal volume of normal saline by intragastric administration. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured before operation and 7 d, 14 d and 28 d after CCI. After behavioral test, DRG of lumbar spinal was obtained from each group, and was used to determine Ca²⁺ concentration by o-cresolphthalein complexone microplating method, and the expression of GAP-43, PKC and CaM at mRNA and protein levels by Western blotting and RT-PCR. RESULTS: Compared with model group, EMA401 significantly increased the TWL and MWT (P<0.05). Meanwhile, EMA401 significantly reduced Ca²⁺ concentration and the expression of GAP-43, PKC and CaM at mRNA and protein levels in the DRG (P<0.05). CONCLUSION: EMA401 may attenuate neuropathic pain of CCI by inhibiting Ca²⁺ concentration and the expression of GAP-43, PKC and CaM.