机构地区:[1]湖北省妇幼保健院妇科,武汉430070 [2]华中科技大学同济医学院附属同济医院中西医结合研究所,武汉430030 [3]华中科技大学同济医学院附属同济医院神经内科,武汉430030
出 处:《中西医结合研究》2011年第6期291-295,共5页Research of Integrated Traditional Chinese and Western Medicine
基 金:国家自然科学基金重大研究计划资助项目(No.90209009);国家重点基础研究发展计划(973计划)资助项目(No.2006CB504502)
摘 要:目的探讨细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)-cAMP反应元件结合蛋白(cyclic AMP response element binding protein,CREB)通路在针刺缓解内脏痛中的作用及缝隙连接蛋白43(connexin43,Cx43)基因敲除对其的影响。方法选用野生型(wide type,WT)和Cx43基因敲除杂合子(heterozygous,HT)小鼠,随机分为6组:HT空白对照组、HT模型组、HT针刺组、WT空白对照组、WT模型组、WT针刺组,建立醋酸致炎性内脏痛模型,采用免疫印迹法(Western blot)观察脊髓背角磷酸化ERK(pERK)和磷酸化CREB(pCREB)的表达。结果 HT和WT空白对照组小鼠脊髓背角pERK和pCREB很少表达,两组间差异无统计学意义(P>0.05)。腹腔注射醋酸能诱导脊髓背角ERK和CREB的磷酸化,与对照组比较差异有统计学意义(P<0.01);HT和WT两组间比较差异无统计学意义(P>0.05)。与模型组比较,WT针刺组小鼠脊髓背角pERK和pCREB表达水平明显降低,差异有统计学意义(P<0.01);HT针刺组小鼠pERK和pCREB表达水平虽然亦有下降趋势,但与模型组比较差异无统计学意义(P>0.05)。HT和WT针刺组两组间差异有统计学意义(P<0.05)。结论①外周伤害性刺激可以诱导ERK-CREB通路的激活;②针刺缓解炎性内脏痛的作用可能与抑制脊髓神经元ERK-CREB通路的激活有关;③敲除Cx43基因影响针刺镇痛作用的机制可能与ERK-CREB通路有关。提示Cx43及以Cx为结构基础的细胞缝隙连接通讯(gap junctional intercellular communication,GJIC)与针刺镇痛效应密切相关。Objective To explore the possible role of extracellular signal-regulated kinase(ERK)and cyclic AMP response element binding protein(CREB)pathway in acupuncture relieving the visceral pain,and the effect of connexin43 gene knockout on it. Methods Wide type(WT)and connexin43 gene knockout mice were randomly divided into 6 groups : heterozygous (HT) control group, HT model group, HT acupuncture group, WT control group, WT model group and WT acupuncture group. Inflammatory visceral pain model was established by intraperitoneal administration of acetic acid. The expression of phosphorylated ERK(pERK)and phosphorylated CREB(pCREB)in the spinal dorsal horn was assessed by Western blot analysis. Results There was no significant difference between HT control group and WT control group mice(P〉0.05) ,in which little pERK and pCREB expressed. Compared to control group,the expression of pERK and pCREB both in HT model group and WT model group mice increased significantly following intraperitoneal acetic acid injection(P〈0.01). And no significant difference was found between HT and WT model group(P〉0.05). Acupuncture could significantly down-regulate pERK and pCREB expression in WT mice as compared to model group(P〈0.01). In HT acupuncture group,the above tendency was al- so seen,but was not statistically significantly different from HT model group. There was significant difference between HT and WT acupuncture groups(P〈0.05). Conclusion Peripheral noxious stimulation could induce the activation of ERK-CREB pathway in the spinal dorsal horn. Acupuncture has a marked antinociceptive effect in visceral pain model mice, which may be related to its effect in suppressing the activation of ERK-CREB pathway in the spinal dorsal horn evoked by noxious stimulation. The mechanism of connexin43 gene knockout on acupuncture analgesia is possibly related with the expression of ERK-CREB in the spinal dorsal horn. These suggest that connex- in43 and gap junctional intercellular communic
关 键 词:细胞外信号调节激酶 CAMP反应元件结合蛋白 针刺镇痛 缝隙连接蛋白43 基因敲除
分 类 号:R245[医药卫生—针灸推拿学]
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