AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied...AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.展开更多
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: control...AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.展开更多
AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-c...AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.展开更多
BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integra...BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.AIM To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.METHODS CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by immunohistochemical staining for Fos.Basic synaptic transmission within the NTS was assessed by electrophysiological recordings.Expression of vesicular glutamate transporters(VGluTs),N-methyl-D-aspartate receptor subtype 2B(NR2B),andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1(GluR1)was analyzed by immunoblotting.Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy.The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.RESULTS TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS.The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats(frequency:5.87±1.12 Hz in CP rats vs 2.55±0.44 Hz in sham rats,P<0.01;amplitude:19.60±1.39 pA in CP rats vs 14.71±1.07 pA in sham rats;P<0.01).CP rats showed upregulated expression of VGluT2,and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS.Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats(abdominal withdraw threshold:7.00±1.02 g in CNQX group,8.00±0.81 g in AP-5 group and 1.10±0.27 g in saline group,P<0.001).Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia(abdominal withdraw threshold:13.67±2.55 g in Gi group,2.00±1.37 g in Gq group,and 2.36±0.67 g in mCherry group,P<0.01).CONCLUSION Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents,which provide novel insights into the central sensitization of painful CP.展开更多
AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was adm...AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.展开更多
目的探讨环磷酸腺苷活化交换蛋白1（Epac1）对大鼠内脏高敏感的调控作用及其机制。方法选择雄性SD大鼠45只,随机分为对照组、模型组、CE3F4组、每组15只。模型组、CE3F4组建立内脏高敏感模型,对照组不建模。标准环境下饲养至出生后第8周...目的探讨环磷酸腺苷活化交换蛋白1（Epac1）对大鼠内脏高敏感的调控作用及其机制。方法选择雄性SD大鼠45只,随机分为对照组、模型组、CE3F4组、每组15只。模型组、CE3F4组建立内脏高敏感模型,对照组不建模。标准环境下饲养至出生后第8周,对照组、模型组鞘内注射生理盐水25μL,CE3F4组鞘内注射0.2nmol/μL CE3F4溶液25μL。鞘内注射第4天采用球囊扩张法扩张结直肠,分别于20、40、60、80 mm Hg压力下行腹壁收缩反射（AWR）评分,同时测量疼痛感觉阈值、最大容量感觉阈值时的压力。应用qRT-PCR及蛋白印迹法检测支配结肠的L5~S1节段背根神经节（DRG）Epac1、蛋白激酶C（PKC）εmRNA和蛋白表达。结果与对照组比较,模型组40、60、80 mm Hg压力时AWR评分升高,疼痛感觉阈值与最大容量感觉阈值时的压力下降（P均〈0.05）,提示成功建立内脏高敏感模型。与模型组比较,CE3F4组在40、60 mm Hg压力时AWR评分显著下降（P均〈0.05）。模型组在疼痛感觉阈值、最大容量感觉阈值时的压力较对照组明显降低（P均〈0.05）,而CE3F4组较模型组明显升高（P均〈0.05）。与对照组比较,模型组DRG的Epac1、PKCεmRNA和蛋白表达均显著升高（P均〈0.05）。与模型组比较,CE3F4组Epac1 mRNA和蛋白表达无明显变化（P均〉0.05）,但PKCεmRNA和蛋白表达显著降低（P均〈0.05）。结论 Epac1可能参与大鼠内脏高敏感的调控,其机制与下游PKCε活化有关。展开更多
基金Supported by National Basic Research Program of China(973 Program)No.2009CB522900 and No.2015CB554501National Natural Science Foundation of China,No.30973784
文摘AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.
文摘AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
基金Supported by National Natural Science Foundation of China,No.81270469Key Medical Personnel of Jiangsu Province,No.RC2011063m
文摘AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.
基金Supported by National Natural Science Foundation of China,No.81620108008Major Research and Development Project of Hainan Province,No.2018153 to Yun-Qing LiTraining Program for Scientific Research Scholars of Fujian Provincial Health and Family Planning Commission,No.2018-ZQN-74 to Ying-Biao Chen
文摘BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.AIM To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.METHODS CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by immunohistochemical staining for Fos.Basic synaptic transmission within the NTS was assessed by electrophysiological recordings.Expression of vesicular glutamate transporters(VGluTs),N-methyl-D-aspartate receptor subtype 2B(NR2B),andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1(GluR1)was analyzed by immunoblotting.Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy.The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.RESULTS TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS.The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats(frequency:5.87±1.12 Hz in CP rats vs 2.55±0.44 Hz in sham rats,P<0.01;amplitude:19.60±1.39 pA in CP rats vs 14.71±1.07 pA in sham rats;P<0.01).CP rats showed upregulated expression of VGluT2,and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS.Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats(abdominal withdraw threshold:7.00±1.02 g in CNQX group,8.00±0.81 g in AP-5 group and 1.10±0.27 g in saline group,P<0.001).Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia(abdominal withdraw threshold:13.67±2.55 g in Gi group,2.00±1.37 g in Gq group,and 2.36±0.67 g in mCherry group,P<0.01).CONCLUSION Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents,which provide novel insights into the central sensitization of painful CP.
文摘AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.
文摘目的探讨环磷酸腺苷活化交换蛋白1（Epac1）对大鼠内脏高敏感的调控作用及其机制。方法选择雄性SD大鼠45只,随机分为对照组、模型组、CE3F4组、每组15只。模型组、CE3F4组建立内脏高敏感模型,对照组不建模。标准环境下饲养至出生后第8周,对照组、模型组鞘内注射生理盐水25μL,CE3F4组鞘内注射0.2nmol/μL CE3F4溶液25μL。鞘内注射第4天采用球囊扩张法扩张结直肠,分别于20、40、60、80 mm Hg压力下行腹壁收缩反射（AWR）评分,同时测量疼痛感觉阈值、最大容量感觉阈值时的压力。应用qRT-PCR及蛋白印迹法检测支配结肠的L5~S1节段背根神经节（DRG）Epac1、蛋白激酶C（PKC）εmRNA和蛋白表达。结果与对照组比较,模型组40、60、80 mm Hg压力时AWR评分升高,疼痛感觉阈值与最大容量感觉阈值时的压力下降（P均〈0.05）,提示成功建立内脏高敏感模型。与模型组比较,CE3F4组在40、60 mm Hg压力时AWR评分显著下降（P均〈0.05）。模型组在疼痛感觉阈值、最大容量感觉阈值时的压力较对照组明显降低（P均〈0.05）,而CE3F4组较模型组明显升高（P均〈0.05）。与对照组比较,模型组DRG的Epac1、PKCεmRNA和蛋白表达均显著升高（P均〈0.05）。与模型组比较,CE3F4组Epac1 mRNA和蛋白表达无明显变化（P均〉0.05）,但PKCεmRNA和蛋白表达显著降低（P均〈0.05）。结论 Epac1可能参与大鼠内脏高敏感的调控,其机制与下游PKCε活化有关。
