快动眼睡眠剥夺对丁酸钠诱导的内脏感觉过敏大鼠模型的调节作用

目的研究丁酸钠灌肠对大鼠内脏感觉功能的影响以及快动眼睡眠剥夺对大鼠内脏感觉功能的调节作用。方法大鼠行丁酸钠溶液灌肠（200mmol／L，6次），对照组行生理盐水灌肠。两组大鼠均在第1次灌肠后的第3、6、9、12、15、18天行结直肠气蠼扩张（CRD），观察大鼠的腹壁回撤反射（AWR）测定内脏感觉功能。丁酸钠灌肠大鼠分为快动眼睡眠剥夺组和对照组。在快动眼睡眠剥夺的第24h、48h、72h行CRD，观察大鼠的腹壁回撤反射（AWR）测定内脏感觉功能。结果第3，6、9、12天，在20、40、60、80mmHg的扩张压力下，丁酸钠灌肠组的AWR评分明显高于生理盐水灌肠组（P＜0．05）。而在第15、18天，丁酸钠灌肠组的AWR评分与对照组无显著性差异（P＞0．05）。快动眼睡眠剥夺的第24h，大鼠对80mmHg扩张刺激的AWR评分明显低于对照组（P＜0．05）；而快动眼睡眠剥夺的第48、72h，大鼠对不同程度扩张刺激的AWR评分均明显低于对照组（P＜0．05）。在快动眼睡眠剥夺的第48、72h大鼠的疼痛感觉阈值升高（P＜0．01）。结论丁酸钠溶液反复灌肠可诱导大鼠内脏感觉过敏；快动眼睡眠剥夺可提高模型鼠的内脏疼痛感觉阈值，降低内脏感觉敏感性。     

REM睡眠剥夺对大鼠内脏感觉影响的研究

目的研究快动眼（rapid eye movement，REM）睡眠剥夺对大鼠内脏感觉功能的影响。方法将24只Sprague-Dawley大鼠随机分为正常对照组（home—eagecontml，HC组）、实验对照组（cage—yokedeontrol，YC组）和REM睡眠剥夺组（sleep deprivation，SD组）。采用花瓶技术对SD组进行REM睡眠剥夺。在REM睡眠剥夺的第12h、24h、48h、72h行结直肠扩张（CRD），观察大鼠的腹壁回撤反射（AWR）以测定内脏感觉功能。结果在REM睡眠剥夺的第12、24h，大鼠对80mmHg扩张刺激的AWR评分明显低于YC及HC组；而REM睡眠剥夺的第48、72h，40mmHg、60mmHg、80mmHg扩张刺激的AWR评分明显低于YC及HC组。在REM睡眠剥夺的第48、72h大鼠的初始感觉阈值及疼痛感觉阈值升高。结论REM睡眠剥夺降低大鼠的内脏感觉功能，且与睡眠剥夺时间相关。     

ZD 7288,an HCN channel blocker,attenuates chronic visceral pain in irritable bowel syndrome-like rats

AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously.Visceral hypersensitivity was evaluated using electromyographic(EMG)responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions(CRD).Abdominal withdrawal reflex(AWR)scores and pain thresholds were also detected in adult rats.Different doses of ZD7288(25,50,and 100 nmol/L)were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.RESULTS:EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats(P<0.05).The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats(P<0.05).Treatment with50-100 nmol/L ZD 7288 significantly inhibited EMG responses(16%-62%,80-20 mmHg CRD,P<0.05)and AWR scores(24%-37%,40-20 mmHg CRD,P<0.05;12%-61%,80-20 mmHg CRD,P<0.05,respectively),and significantly increased pain thresholds(32%-77%,P<0.05).CONCLUSION:Spinal HCN channels may play an important role in chronic visceral hypersensitivity.     

丁酸钠溶液灌肠对大鼠内脏感觉的影响

对于肠易激综合征（IBS）内脏感觉功能异常的研究，需建立合适的动物模型。目的：以丁酸钠溶液灌肠建立大鼠结肠感觉过敏模型，观察其内脏感觉功能和结肠黏膜改变。方法：16只大鼠随机分为实验组和对照组。实验组予1 ml 200mmol／L丁酸钠溶液灌肠，对照组予1 ml 0.9％NaCl溶液灌肠，每天2次，连续3d。分别于灌肠前和实验开始后第3、6、9、12、15、18d行结直肠扩张（CRD），观察腹壁回撤反射（AWR）评分和内脏感觉压力闽值，以反映内脏感觉功能。实验结束后处死大鼠，行结肠黏膜大体形态观察和组织学检查。结果：实验第3-12d．实验组不同CRD压力下AWR评分均显著高于对照组（P〈0.05），疼痛感觉压力阈值显著低于对照组（P〈0.05）；第15-18d，上述指标恢复至初始状态。实验结束后,实验组与对照组结肠黏膜大体形态和组织学改变均无明显差异。结论：丁酸钠溶液反复灌肠可诱导大鼠结肠感觉过敏，内脏感觉功能恢复后，结肠黏膜改变同步恢复。该模型可用于IBS病理生理机制的研究。     

焦虑大鼠内脏敏感性增高以及行直结肠扩张后血清皮质酮的变化及意义

目的内脏高敏感性是肠易激综合征( 1BS)症状最重要的病理生理机制之一,焦虑可能与内脏高敏的发生密切相关。本研究旨在探讨焦虑对大鼠直结肠敏感性的作用以及血清皮质酮与内脏高敏的关系。方法Wistar大鼠随机分为对照组和焦虑组两组,通过对大鼠行空瓶刺激2周建立以焦虑为主要表现的慢性情绪应激模型。造模期间,观察大鼠的攻击、探究和修饰三种行为,对其进行情绪性行为学分析。造模结束后,以腹部回缩反射(AWR)评分为指标观察大鼠对直结肠气囊扩张(CRD)的反应性,评估内脏敏感性。然后将两组各随机分为扩张组和非扩张组,对扩张组行CRD ,并取血清,对血清皮质酮定量测定。结果空瓶刺激期间,同对照组相比,焦虑组探究、攻击行为明显增多,修饰行为减少(P <0 0 1)。焦虑组在2 0mmHg、40mmHg、60mmHg和80mmHg的扩张压力下的AWR评分均显著高于对照组(P <0 0 1)。焦虑组与对照组相比血清皮质酮水平明显升高(P <0 0 1) ,但各组扩张后皮质酮水平较扩张前仅有轻微升高,无显著差异(P >0 0 5 )。结论焦虑对IBS内脏高敏起一定作用,其发挥作用的机制可能并非单一通过下丘脑_垂体_肾上腺皮质系统(HPA轴)来实现,推测还可能与脑内单胺类神经递质NE浓度的改变有关。     

急性和慢性束缚应激对大鼠内脏敏感性的影响

目的了解急性和慢性求缚应激对大鼠内脏敏感性的影响和持续时间。方法成年SD大鼠随机分为3组：对照组（没有束缚应激），急性部分束缚应激组（单次2h的束缚应激）和慢性部分束缚应激组（连续束缚应激3天，每天2h），通过腹壁回撤反应（AWR）评分评估应激前后不同时间点大鼠对结直肠扩张（CRD）的内脏敏感性。结果①在扩张压力20mmHg和40mmHg时，急慢性束缚应激组的AWR评分均显著高于应激前基础水平（Od）（P〈0．05），但在60，80mmHg压力时各组的AWR评分均无显著差异；②急性束缚组在应激后24h和应激后第7天，AWR评分显著下降（P〈0．05）；③慢性束缚组在末次应激后24h，AWR评分仍维持增高水平，但在第7天时AWR评分回到基础水平。结论急性和慢性束缚应激郜可以导致大鼠内脏敏感性增高，但其作用可能是短暂的。     

Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity

AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7^th week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05).CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.     

肠康方对肠易激综合征内脏高敏感模型大鼠的作用

[目的]探讨肠康方对肠易激综合征(IBS)内脏高敏感模型大鼠的作用.[方法]制备肠易激综合征内脏高敏感模型,将72只Sprague-Dawley大鼠随机分为6组,即模型组,空白对照组,阳性药物对照组,肠康方高、中、低剂量组.在造模第60天开始灌胃给药或0.9％氯化钠溶液共10d,干预后通过腹肌回缩反射(AWR)半定量评分测定大鼠内脏敏感性.[结果]不同压力下模型组AWR评分显著高于空白对照组,肠康方高、中、低剂量组治疗后AWR评分均显著低于模型组(P＜0.05或P＜0.01).[结论]肠康方可通过改善内脏高敏感治疗IBS.     

Effects of octreotide on responses to colorectal distension in the rat

BACKGROUND AND AIMS: It has been suggested that the analgesic effect of the somatostatin analogue octreotide in visceral pain involves peripheral mechanisms. We evaluated the effect of octreotide on responses to noxious colorectal distension in rats. METHODS: In a behavioural study, pressor and electromyographic responses to colorectal distension were evaluated before and after intravenous or intrathecal administration of octreotide. In pelvic nerve afferent fibre recordings, responses of mechanosensitive fibres innervating the colon to noxious colorectal distension (80 mm Hg, 30 seconds) were tested before and after octreotide. RESULTS: Octreotide was ineffective in attenuating responses to colorectal distension in either normal or acetic acid inflamed colon when administered intravenously but attenuated responses when given intrathecally. Administration of octreotide over a broad dose range (0.5 microg/kg to 2.4 mg/kg) did not alter responses of afferent fibres to noxious colorectal distension in untreated, or acetic acid or zymosan treated colons. CONCLUSIONS: In the rat, octreotide has no peripheral (pelvic nerve) modulatory action in visceral nociception. The antinociceptive effect of octreotide in this model of visceral nociception is mediated by an action at central sites.     

Peripheral corticotropin releasing hormone mediates post-inflammatory visceral hypersensitivity in rats

AIM： To investigate whether peripheral corticotropin releasing hormone （CRH）, which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis.
METHODS： We measured mucosal myeloperoxidase （MPO） activity as a marker of inflammation, plasma CRH level, and abdominal withdrawal reflex （AWR） to colorectal distension as a visceral nociceptive response at 2, 7 and 14 d after the induction of colitis with 4% acetic acid.
RESULTS： Colonic inflammation, quantified by MPO activity, significantly increased on d 2 and subsided thereafter, which indicated a resolution of inflammation within 7 d. On the contrary, plasma CRH level and AWR score were increased on d 2, remained high on d 7, and returned to control level on d 14. Intraperitoneal injection of a CRH antagonist, astressin （30 μg/kg）, significantly attenuated the post-inflammatory visceral hypersensitivity on d 7. Furthermore, intraperitoneal administration of CRH （3 and 10 μg/kg） mimicked the post-inflammatory visceral hypersensitivity in naive rats.
CONCLUSION： These results suggest that increased peripheral CRH mediates the enhanced visceral nociception in rats recovered from experimental colitis.     

慢性内脏高敏性大鼠结肠内P物质及其NK1受体表达的改变

目的　研究慢性应激刺激所致内脏高敏性大鼠和正常大鼠结肠内P物质 (substanup)及其NK1受体表达的改变 ,探讨内脏高敏感性产生的可能机制。方法　 40只新生SD大鼠 ,随机分为 2组 :慢性应激模型组、正常对照组 ,每组 2 0只。模型组大鼠在出生后第 8天到 2 1天 ,每天接受结直肠扩张刺激 ;分别在第 8周、12周观察大鼠的腹部回缩反射 (AWR)和玻璃小球排出情况 ,进行肠道敏感性评估 :采用RT PCR方法检测二组大鼠结肠组织内P物质及其NK1受体mRNA的表达 ,并运用免疫组化SABC法观察NK1受体的分布。结果　模型组较正常对照组大鼠腹部收缩阈值明显降低 (P <0 .0 1) ,玻璃小球排出时间缩短 (P <0 .0 1) ;P物质及其NKl受体mRNA的表达明显增加 (P <0 .0 1) ,NK1受体免疫反应阳性产物显著浓密 ,以平滑肌层和黏膜层为著。结论　SP及其NK1受体表达增加在大鼠肠道高敏感性、动力紊乱的产生机制中可能起重要作用     

褪黑激素及其受体对腹泻表现内脏高敏感大鼠胃肠道动力的影响

背景:肠易激综合征(IBS)的发病机制尚不完全清楚,褪黑激素(MT)可能参与IBS的病理生理。目的:探讨血清MT以及肠道褪黑激素受体(MR)在腹泻型IBS(IBS-D)发病机制中的意义。方法:45只Sprague-Dawley大鼠随机分为模型组、对照组以及模型治疗组。予大鼠球囊结直肠扩张,以制备腹泻表现内脏高敏感模型。造模后,模型治疗组大鼠每天给予MT 0.3 mg/kg灌胃,连续2周。实验第54 d处死大鼠。以腹壁回撤反射(AWR)评分评估内脏敏感性;观察大便性状,行Bristol评分;免疫组化法检测回盲部以及乙状结肠MR表达;ELISA法测定血清MT水平。结果:与对照组相比,模型组大鼠AWR评分、Bristol评分、肠道MR表达均显著升高,而血清MT水平显著降低(P0.05)。经MT治疗后,上述指标均显著改善(P0.05)。结论:肠道MR表达增强和血清MT水平降低可调节胃肠道运动,可能参与IBS-D的发生。     

Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by noxious colorectal distention in rat

AIM: To observe how acupuncture stimulation influences the visceral nociception in rat and to clarify the interactions between acupuncture or somatic input and visceral nociceptive inputs in the spinal dorsal horn. These will provide scientific base for illustrating the mechanism of acupuncture on visceral pain. METHODS: Experiments were performed on Sprague-Dawley rats and the visceral nociceptive stimulus was generated by colorectal distention (CRD). Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in L1-3 spinal dorsal horn. Acupuncture stimulation was applied at contralateral heterotopic acupoint and ipsilateral homotopic acupoint, both of which were innervated by the same segments that innervate also the colorectal-gut. RESULTS: The visceral nociception could be inhibited at the spinal level by the heterotopic somatic mechanical stimulation and acupuncture. The maximal inhibition was induced by acupuncture or the somatic noxious stimulation at spinal dorsal horn level with inhibiting rate of 68.61% and 60.79%, respectively (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block) both spontaneous activity and responses to CRD increased significantly in 16/20 units examined, indicating the existence of tonic descending inhibition. The inhibition of acupuncture on the noxious CRD disappeared totally in the reversible spinalized rats (P<0.001). CONCLUSION: The inputs of noxious CRD and acupuncture may interact at the spinal level. The nociceptive visceral inputs could be inhibited by acupuncture applied to hetero-topic acupoint. The effect indicates that the spinal dorsal horn plays a significant role in mediating the inhibition of acupuncture and somatic stimulation on the neuronal response to the noxious visceral stimulation and the inhibition is modulated by upper cervical cord and/or supra-spinal center.     

去甲肾上腺素在快动眼睡眠剥夺降低大鼠内脏感觉功能中的作用

目的 研究去甲肾上腺素(NE)在快动眼(REM)睡眠剥夺降低大鼠内脏感觉功能中的作用.方法 大鼠随机分为实验对照组(YC)、REM睡眠剥夺组(SD)、REM睡眠剥夺后育亨宾干预组(YSD).采用"花瓶技术"对SD组及YSD组进行REM睡眠剥夺48 h,YSD组在48 h时给予腹腔注射育亨宾.造模完成后行结直肠扩张(CRD),观察各组大鼠疼痛感觉阈值,记录大鼠的腹壁肌电图了解腹壁肌的放电次数.采用RT-PCR半定量检测丘脑及肠道组织单胺氧化酶A(MAO-A)和酪氨酸羟化酶(TH)基因表达水平.结果 REM睡眠剥夺48 h时各组大鼠在20、40、60、80 mm Hg(1 mm Hg=0.133 kPa)扩张压力下的腹壁肌放电结果显示:(1)SD组大鼠扩张刺激后的腹壁肌放电次数(178±98、839±323、1331±444、1703±478)显著低于YC组(413±171、1400±245、2070±386、2510±469),且疼痛感觉压力阈值显著增高(P＜0.05);(2)YSD组大鼠扩张刺激后的腹壁肌放电次数(415±212、1490±227、2129±435、2381±399)明显高于SD组,且疼痛感觉压力阈值显著降低(P＜0.05);(3)SD组REM睡眠剥夺48 h后,丘脑及肠道中MAO-A mRNA的水平明显低于YC组(P＜0.05),而TH mRNA的表达显著增高(P＜0.05).结论 REM睡眠剥夺降低大鼠的内脏感觉功能与NE合成增加及代谢减少有关,α2受体拮抗剂可提高大鼠的内脏感觉功能.     

Effect of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension

BACKGROUND: Acute mucosal inflammation may initiate alterations of visceral sensory function. However, experimental studies on the potential effects of a transient inflammation on visceral sensitivity are lacking. METHODS: We performed colorectal distensions with a barostat device in fasted, conscious, male Lewis rats (n = 20) and assessed the nociceptive response (visceromotor response; VMR) to tonic colorectal distension (CRD) (60 mmHg/3 min) by abdominal-wall electromyography. Measurements were taken before and 3, 5 and 14 days after induction of a transient and self-limiting colitis by instillation of trinitrobenzenesulphonic acid (TNB)/ethanol (or saline as control). Tissue samples from paired controls were obtained to assess histological tissue alterations. RESULTS: TNB/ethanol but not saline induced an acute colitis, with most severe histological lesions occurring 5 days after instillation. After 14 days, there was no histological evidence for persisting mucosal alterations. Five days after induction of TNB/ethanol colitis, the VMR to CRD reached a transient increase (P < 0.05 v. baseline), which returned to baseline levels by day 14. In control experiments (rectal saline instillation), the VMR to CRD decreased significantly compared with baseline values (P < 0.05). CONCLUSION: Following an acute colitis due to single colorectal instillation of TNB/ethanol, histological changes are associated with an enhanced nociceptive response to CRD.     

The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats

BACKGROUND & AIMS: Robust chemical or mechanical irritation of the colon of neonatal rats leads to chronic visceral hypersensitivity. The clinical and physiologic relevance of such noxious stimulation in the context of human irritable bowel syndrome is questionable. The aims of this study were to determine whether mild chemical irritation of the colon of neonatal rats produced persistent changes in visceral sensitivity and to evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in the initiation and maintenance of visceral hypersensitivity. METHODS: Ten-day-old rat pups received an intracolonic infusion of 0.5% acetic acid in saline. TRPV1 inhibitors were administered 30 minutes before acetic acid sensitization. Sensitivity of the colon to balloon distention (CRD) in adults was measured by grading their abdominal withdrawal reflex and electromyographic responses. In adult rats, TRPV1 antagonist was injected intraperitoneally 30 minutes before CRD. RESULTS: Neonatal acetic acid treatment resulted in higher sensitivity to CRD in adult rats compared with controls in the absence of histopathologic signs of inflammation. Treatment of colons of adult rats with acetic acid did not produce persistent sensitization. Antagonism of the TRPV1 before neonatal administration of acetic acid and after established visceral hypersensitivity attenuated sensitivity to CRD. TRPV1 expression was increased in dorsal root ganglia-containing colon afferent neurons. CONCLUSIONS: We have described a new model for persistent colonic sensory dysfunction following a transient noxious stimulus in the neonatal period and a potentially important role for TRPV1 in initiation and maintenance of persistent visceral hypersensitivity.     

Role of nesfatin-1 in a rat model of visceral hypersensitivity

AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/ nucleobindin-2 (NUCB2), 50 μg of α-helical cortico-tropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05). CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, which may be implicated in brain C     

肠道炎症诱导的内脏和躯体痛觉过敏

背景：慢性腹痛是功能性胃肠病患者常见症状之一,此类患者亦可同时具有较明显的躯体症状。内脏和躯体症状并存极大影响了患者的生活质量,并增加就医负担。目的：观察肠道炎症后大鼠内脏和躯体痛觉,探究两者间的联系和可能的共同发病机制。方法：80只雄性Sprague—Dawley大鼠随机分为模型组、溶剂对照组和阴性对照组,分别给予20mgTNBS／乙醇混合液、50％乙醇和0．9％NaCl溶液灌肠。灌肠8周后,行不同压力结直肠扩张（CRD）诱导内脏运动反射（VMR）以评估大鼠内脏痛觉。以机械缩足反射阈值（MWT）和甩尾反射潜伏期（TFL）评估躯体痛觉。结果：造模8周后模型组大鼠结肠黏膜病理表现与两组对照组相比无明显差异,未见明显溃疡和炎性细胞浸润。与两组对照组相比,32．5％的模型组大鼠内脏痛觉阈值明显下降（P〈0．001）,且这部分内脏痛觉高敏感的模型组大鼠MWT和TFL均明显降低（P〈0．001）。结论：本研究建立的动物模型模拟了感染后肠易激综合征状态,TNBS诱导的肠道炎症同时导致了大鼠内脏和躯体痛觉过敏,有助于进一步探究内脏和躯体痛觉过敏的共同发病机制。     

先天抑郁大鼠内脏敏感性研究

目的 比较先天抑郁Fawn-Hooded(FH/Wjd)大鼠与Sprague-Dawley(SD)大鼠的内脏敏感性,探讨FH/Wjd大鼠作为精神障碍与肠易激综合征共病模型的可行性.方法 采用强迫游泳实验(FST)和糖水实验(SPT)验证FH/Wjd大鼠的抑郁特性.通过腹壁回撤反射(AWR)评估大鼠对不同压力结直肠扩张(CRD)的敏感性.免疫组织化学法检测大鼠结肠5-HT表达水平及结肠、大脑前额叶下边缘皮质(IL)、前边缘皮质(PrL)、前喙扣带回皮质(rACC)区域的c-fos表达水平.结果 FST中FH/Wjd大鼠水中静止时间显著长于SD大鼠(t＝8.931,P＝0.000).SPT中FH/Wjd大鼠糖水饮用量占总饮水量的比例显著低于SD大鼠(t＝4.155,P＝0.001).FH/Wjd大鼠在各CRD压力梯度(20、40、60、80 mm Hg,1 mm Hg=0.133 kPa)下的AWR评分均显著高于SD大鼠(t值分别＝-2.697、-3.464、-6.822、-3.976,P值分别＝0.022、0.006、0.000、0.003).FH/Wjd大鼠对照组结肠5-HT表达水平高于SD大鼠对照组(t=-11.371,P=0.000).FH/Wjd大鼠扩张组和SD大鼠扩张组结肠5-HT表达水平均较各自的对照组上升,且FH/Wjd大鼠表达水平高于SD大鼠(t＝-3.364,P＝0.007).FH/Wjd大鼠对照组和SD大鼠对照组结肠、前额叶各脑区c-fos表达水平差异无统计学意义(结肠:t＝-0.129、P＝0.900;IL:t＝-1.316、P＝0.218;PrL:t＝1.241、P＝0.243;rACC:t＝2.151、P＝0.057).FH/Wjd大鼠扩张组和SD大鼠扩张组结肠与前额叶脑区c-fos 表达水平均较各自的对照组显著上升,且FH/Wjd大鼠表达水平高于SD大鼠(结肠:t＝-5.864、P＝0.000;IL:t＝-2.530、P＝0.030;PrL:t＝-7.039,P＝0.000;rACC:t＝-6.489、P＝0.000).结论 先天抑郁FH/Wjd大鼠存在内脏高敏感性,其肠道高表达5-HT及结肠和大脑IL、PrL、rACC 区域对内脏伤害性刺激的高反应性.有可能作为精神障碍和肠易激综合征共病的动物模型.

Abstract：

Objective To explore the feasibility of inherent depressive Fawn-Hooded (FH/Wjd)rats as a comorbidity model of mental disorder and irritable bowel syndrome (IBS) by comparing visceral sensitivity of FH/Wjd rats and Sprague-Dawley (SD) rats. Methods Depression trait of FH/Wjd rats was validated through forced swimming test (FST) and sucrose preference test (SPT).Visceral sensitivity to colorectal distention (CRD) under various pressures was assessed by abdominal withdrawal reflex (AWR). The expression of 5-HT in rats' colon,c-fos expression in colon and brain areas of infralimbic cortex (IL),prelimbic cortex (PrL) and rostral anterior cingulated cortex (rACC)was tested with immunohistochemistry. Results FST indicated that the immobility time of FH/Wjd rats was significantly longer than that in SD rats (t=-8. 931,P＜0. 01). SPT showed that the ratio of sucrose water in total liquid consumed was significantly lower in FH/Wjd rats than that of SD rats(t=4. 155,P=0. 01). At each CRD pressure gradient (20,40,60 and 80 mm Hg,1 mm Hg=0. 133kPa),AWR score was all significantly higher in FH/Wjd rats than that of SD rats (t=-2. 697,-3.464,-6.822 and -3. 976,P=0. 022,0.006,0.000 and 0.003). The expression level of 5-HT in FH/Wjd rats' control group was significantly higher than that of SD rats' control group (t=-11.371,P=0. 000). Compared with their own control group,5-HT expression increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (t= -3. 364,P= 0. 007). There was no significant difference of c-fos expression in colon and prefrontal brain areas between FH/Wjd rats' control group and SD rats'control group (colon:t=-0. 129,P= 0. 900;IL:t=-1. 316,P= 0. 218;PrL:t=1. 241,P = 0. 243;rACC:t=2. 151,P = 0. 057). Compared with their own control group,the expression of c-fos in colon and prefrontal brain areas significantly increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (colon: t=- 5.864,P= 0.000;IL:t=-2. 530,P = 0. 030;PrL:t=-7. 039,P= 0. 000;rACC:t=-6. 489,P=0. 000). Conclusions Inherent depressive FH/Wjd rats present visceral hypersensitivity. Meanwhile,the expression of 5-HT in colon is high,and with hyperreactivity to visceral noxious stimuli in colon and brain IL,PrL,and rACC areas. FH/Wjd rats might be a comorbidity animal model of mental disorder and IBS.     

Acute Colitis Enhances Responsiveness of Lumbosacral Spinal Neurons to Colorectal Distension in Rats

Aim of this study was to examine excitability and responsiveness of lumbosacral spinal neurons to colorectal distension (CRD) in rats with colitis induced by dextran sulphate sodium (DSS). Extracellular potentials of single L6-S2 spinal neurons were recorded in pentobarbital anesthetized and paralyzed rats. Results showed that 40/154 (26%) and 53/156 (34%) neurons responded to noxious CRD (80 mmHg, 20 s) in DSS-treated and control animals, respectively. Neurons with long-lasting and low-threshold excitatory responses to CRD were more frequently encountered in DSS-treated than in control groups (P < 0.05). The mean maximal excitatory responses of neurons to noxious CRD in DSS-treated animals were significantly greater and the duration of responses was longer than those in control animals (P < 0.05). It was suggested that lumbosacral spinal neurons with colorectal input had increased excitability and responsiveness following colitis, which might play an important role in development of colonic hypersensitivity and viscerosomatic referred pain.