Mu阿片受体在大鼠“泻剂结肠”肠道低反应中的作用

目的：研究Mu阿片受体对“泻剂结肠”大鼠结肠动力的影响。“泻剂结肠”大鼠肠道阿片受体含量的变化。方法：以“泻剂结肠”为模型，用刺激离体肌条收缩反应试验，放射性配体结合等方法。结果：外源性增加DAMGO明显抑制电刺激“泻剂结肠”大鼠离体肌体收缩反应，收缩波振幅降低，这种抑制作用是剂量相关，mu阿片受体拮抗剂Naloxone明显加强电刺激“泻剂结肠”大鼠离体肌条收缩反应，收缩波振增加，与正常组相比，“泻剂结肠”大鼠肠道mu阿片受体含量增加，结论：内源性阿片肽通过阿片受体介导参与了慢传输性便秘肠道动力的调控，主要是通过mu阿片受体。     

"泻剂结肠"大鼠的结肠肌电生理变化及其意义

目的 探讨慢性输型便秘（STC）的发生机理。方法 建立大鼠“泻剂结肠”模型,并测定其结肠的肌电生理活动变化。结果 “泻剂结肠”大鼠的结肠慢波频率减慢,振幅降低;餐后峰电位发放明显少于正常对照组且持续时间短,表明胃结肠反射明显减弱。结论 该研究结果提示,长期服用接触性泻剂对结肠肠神经系统有损害作用,这在STC的发生机理中可能具有重要意义。     

慢传输性便秘结肠阿片受体的病理生理改变

目的探讨慢传输性便秘(STC)的发病机制和病理生理改变。方法应用放射配体结合分析法,检测患者结肠mu、kappa阿片受体,观察其含量变化。结果STC患者结肠mu阿片受体的最大结合数(Bmax)和解离常数(KD)比正常对照组明显增加(Bmax400.950比96.304pmol,KD431.314比179.839pmol);kappa阿片受体含量检测亦有类似结果(Bmax:375.073比45.264pmol,KD485.407比141.016pmol)。结论STC患者阿片受体含量增加,内源性阿片肽活性增加。提示采用阿片受体拮抗剂可能是治疗STC的一个新途径。     

Cajal间质细胞在大鼠"泻剂结肠"结肠肌电变化中的作用

目的　研究长期服用接触性泻剂对大鼠结肠肌电的影响 ,探讨Cajal间质细胞 (ICC)在“泻剂结肠”肌电变化中的作用。方法　 32只大鼠随机分为 2组 ,实验组饲以含酚酞饲料 ,3个月后测定结肠慢波频率及振幅 ;用碘化锌 锇酸法 (ZIO)观察肌间丛ICC变化 ,透射电镜观察肌间丛神经和ICC的超微结构变化。结果　“泻剂结肠”结肠慢波频率明显减慢 (P <0 .0 5 ) ,肌间丛ICC分布不均匀 ,突起连接杂乱 ;电镜下见肌间丛神经轴突空化 ,ICC样细胞变性。结论　长期服用酚酞可导致结肠慢波频率减慢 ,其可能机理为肌间丛神经及ICC变性所引起     

Cajal间质细胞在大鼠“泻剂结肠”结肠肌电变化中的 …

目的 研究长期服用接触性泻剂对大鼠结肠肌电的影响，探讨Ｃａｊａｌ间质细胞（ＩＣＣ）在“泻剂结肠”肌电变化中的作用。方法 ３２只大鼠随机分为２组，实验组饲以含酚酞饲料，３个月后测定结肠慢波频率及振幅；用碘化锌－锇酸法（ＺＩＯ）观察肌间丛ＩＣＣ变化，透射电镜观察肌间丛神经和ＩＣＣ的超微结构变化。结果“泻剂结肠”结肠慢波频率明显减慢（Ｐ〈０．０５），肌间丛ＩＣＣ分布不均匀，突起连接杂乱；电镜下见肌间丛神     

结肠慢传输性便秘外科治疗国内外进展

结肠慢传输性便秘(colon slow transit constipation,CSTC)又被称为慢通过性便秘或结肠无力(colonic inertia),是指结肠传输功能障碍,肠内容物通过缓慢所引起的便秘。该病病因不清,症状顽固,影响因素较多。尽管结肠次全(全)切除术对大部分患者取得了较好的效果,但怎样更精确全面地诊断结肠慢传输性便秘,以便选择合适的手术方式从而取得更好的效果;怎样探索结肠慢传输性便秘的发病机理从而在根本上进行防治,仍然是目前这一领域研究的热点。现就结肠慢传输性便秘外科治疗的手术指征、手术方式的选择以及疗效谈谈笔者的一些看法,不足之处请各…     

结肠慢传输性便秘胃肠动力改变的研究进展

结肠慢传输性便秘 (S1 ow Transit Constipa-tion,STC)是因结肠传输功能减弱致使肠内容物滞留于结肠而引起的顽固性便秘 ,病因不清 ,症状顽固 ,治疗困难。随着社会老龄化、现代生活节奏和饮食习惯的改变 ,STC日益成为影响现代人生活质量的重要疾病之一。国内戴菲等 [1] 对 1 5 2 5名健康人群调查发现 ,慢性功能便秘 (Chronic FunctionalConstipation,CFC)占 9. 1 8%,其中 STC占 CFC的 45 %。 1 90 8年 ,Anbuthnot Lane[2 ] 首先提出全结肠切除、回直肠吻合术治疗 STC,近年来逐渐出现了一些改进的术式 ,并取得了良好的疗效。但是 …     

结肠慢传输性便秘外科治疗中的热点问题

结肠慢传输性便秘(colon slow transit constipation,CSTC)是以结肠动力减弱为特征的顽固性便秘,表现为结肠传输减慢、无便意、大便次数明显减少。其发病的主要机制与结肠巨大迁移性收缩波的减少有关,而后者又受肠道平滑肌、肠神经系统和内分泌系统综合调控。该病症状顽固,内科治疗效果不佳,大部分患者最终需要手术切除结肠。多数经手术治疗虽可取得满意效果,但术后腹泻、粘连性肠梗阻、便秘复发依然是外科治疗中所面临的棘手问题。另外,结肠慢传输性便秘是功能性疾病,本身不危及患者生命,患者求助于手术是为了提高生活质量。因此,对手术结果要求很高,不但希望取得满意的治疗效果,恢复良好的排便和控便功能,同时也希望避免出现各种并发症。     

慢传输性便秘结肠神经系统的病理生理改变

目的：了解慢性输性便秘（STC）结肠壁神经系统的病理改变。方法：用免疫组化法检测了慢性输性便秘病人结肠肠壁神经元凋亡现象。结果：STC患者结肠壁神经元有凋亡现象发生，神经元内bcl-2含量下降，而bax无显著变化。结论：这种不恰当的细胞死亡－－病理性神经元凋亡可能在STC的发病过程中具有重要意义，提示通过抑制凋亡的发生是预防和治疗STC的一个有效途径。     

阿片受体在缺血预处理中的作用

目的　研究阿片受体激动在缺血预处理限制心肌梗死(心梗)范围作用中的地位。方法　建立在体家兔心脏缺血再灌注模型,观察阿片受体拮抗剂纳洛酮对缺血预处理心肌保护作用的影响。在离体兔心模型上,观察阿片受体激动剂吗啡代替短暂缺血刺激,对随后发生的急性心梗范围的影响,并用纳洛酮及蛋白激酶C阻断剂Chelerythrine分别进行干预。电镜观察吗啡预处理对离体心脏缺血心肌超微结构改变的影响。结果　在体心脏模型上,5min缺血及10min再灌注的预处理可显著缩小随后30min缺血引起的心梗范围(P＜0.01);在预处理前10min或30min、缺血前5min给予纳洛酮均可使预处理所产生的限制心梗范围的作用消失。离体心脏经历5min全心缺血及10min再灌注的预处理后,可缩小心梗范围(P＜0.05);在缺血前如给予吗啡预灌注15min,亦可缩小心梗范围(P＜0.05),其作用可被纳络酮或Chelerythrine分别阻断。30min缺血后心肌线粒体等超微结构严重受损,如给吗啡预灌流,心肌损伤明显减轻。结论　阿片受体激动参与了缺血预处理的心肌保护;吗啡预处理可以减轻缺血心肌损伤及产生限制心梗范围的心肌保护作用;吗啡是通过心脏局部的阿片受体介导,激活蛋白激酶C从而产生心肌保护作用。     

急、慢性吗啡依赖对大鼠脑组织μ阿片受体的调节差异

目的 观察急、慢性吗啡依赖时大鼠脑组织μ阿片受体（MOR）的调节及基因表达,探讨急、慢性吗啡依赖对MOR调节的差异性。方法40只SD大鼠随机分为对照组、急性依赖组、慢性依赖组、急性戒断组、慢性戒断组。急性依赖组大鼠背部皮下注射5mg/kg吗啡8次,间隔2h;慢性依赖组大鼠按小剂量递增法背部皮下注射吗啡,剂量为5、10、20、40、50、60mg·kg-1·d-1,每日3次（8:00,15:00,22:00）共6d。急、慢性戒断组在末次给药3h后腹腔注射5mg/kg纳洛酮,催促戒断24h。完成处置程序30min后,取脑组织,以3H-DAMGO进行Scatchard分析求出MOR的Bmax和Kd值,采用RT-PCR方法半定量测定MOR mRNA的表达。结果 1.急性吗啡依赖时大鼠脑组织MOR Bmax显著增高,亲和力显著下降,戒断后Bmax迅速恢复,而亲和力仍未能回到正常水平;吗啡慢性依赖时MOR的Bmax非常显著地下调,戒断后仍低于对照组,Kd值未发生明显改变。2.急性吗啡依赖使 MOR mRNA的表达非常显著地增高,戒断后迅速恢复,而吗啡慢性诱导无论依赖还是戒断状态,MOR mRNA的水平均明显低于正常。结论 急、慢性吗啡依赖对大鼠脑组织 MOR的调节方向不同,它们有着相类似的受体后机制。     

Contribution of peripheral opioid receptors to the trimebutine-induced contractions of the proximal colon in anesthetized rats

In this study we investigated the involvement of opioid receptors in the contractile response to trimebutine using with the proximal colon of anesthetized rats. Trimebutine (3 mg/kg i.v.) enhanced spontaneous contractions of the proximal colon in anesthetized rats. The contractile response was partially inhibited by intravenous administration of an opioid antagonist, naloxone at 1 approximately 30 micrograms/kg, but was hardly depressed by intracisternal administration of naloxone (30 micrograms/kg). Morphine (30 micrograms/kg i.v.) evoked colonic contractions which were abolished by intravenous naloxone (30 micrograms/kg). These results suggest that the colonic contractions evoked by trimebutine in anesthetized rats are, in part, mediated by peripheral opioid receptors.     

Activation of opioid mu receptors in caudal medullary raphe region inhibits the ventilatory response to hypercapnia in anesthetized rats

BACKGROUND:: Opioids, extensively used as analgesics, markedly depress ventilation, particularly the ventilatory responsiveness to hypercapnia in humans and animals predominantly via acting on mu receptors. The medullary raphe region (MRR) contains abundant mu receptors responsible for analgesia and is also an important central area involving carbon dioxide chemoreception and contributing to the ventilatory responsiveness to hypercapnia. Therefore, the authors asked whether activation of mu receptors in the caudal, medial, or rostral MRR depressed ventilation and the response to hypercapnia, respectively. METHODS:: Experiments were conducted in 32 anesthetized and spontaneously breathing rats. Ventilation and it response to progressive hypercapnia were recorded. The slopes obtained from plotting minute ventilation, respiratory frequency, and tidal volume against the corresponding levels of end-tidal pressure of carbon dioxide were used as the indices of the respiratory responsiveness to carbon dioxide. DAMGO ([d-Ala2, N-Me-Phe4, Gly-ol]-enkephalin), a mu-receptor agonist, was systemically administered (100 mug/kg) before and/or after local injection of CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (100 ng/100 nl), a mu-receptor antagonist, into the caudal MRR, or locally administered (35 ng/100 nl) into the MRR subnuclei. RESULTS:: The authors found that systemic DAMGO significantly inhibited ventilation and the response to carbon dioxide by 20% and 31%, respectively, and these responses were significantly diminished to 11% and 14% after pretreatment of the caudal MRR with CTAP. Local administration of DAMGO into the caudal MRR also reduced ventilation and the response to carbon dioxide by 22% and 28%, respectively. In sharp contrast, these responses were not observed when the DAMGO microinjection was made in the middle MRR or rostral MRR. CONCLUSIONS:: These results lead to the conclusion that mu receptors in the caudal MRR rather than the middle MRR or rostral MRR are important but not exclusive for attenuating the hypercapnic ventilatory response.     

结肠瓣膜成形术诱导SD大鼠短肠综合征模型结肠上皮化生的机制研究

目的 结肠瓣膜成形术可以使瓣膜前结肠上皮具有类似小肠的吸收功能,本研究拟进一步阐明结肠瓣膜成形术诱导结肠上皮向小肠上皮化生的机制。方法 将40只大鼠随机分配到两组（各20只）,对照组大鼠切除80%小肠,实验组同时行结肠瓣膜成形术。实验后30周处死大鼠,取回肠、瓣膜前结肠及瓣膜后结肠作检测。原位荧光免疫组化法检测肠上皮细胞内Wnt7b蛋白和β-catenin蛋白。结果 实验组大鼠比对照组的大鼠重。HE染色光镜检查发现瓣膜近端的结肠具有类似小肠上皮的特征（上皮增厚、肠隐窝增长以及杯状细胞减少）。免疫组化检查发现瓣膜近端结肠上皮的Wnt7b蛋白和β-catenin蛋白比瓣膜远端结肠上皮的大幅增多。结论 结肠瓣膜成形术促进结肠上皮的吸收功能,其机制很可能是Wnt/β-catenin通路介导的肠上皮干细胞再生。     

Antinociceptive effect of morphine, but not mu opioid receptor number, is attenuated in the spinal cord of diabetic rats

BACKGROUND: The mechanisms of decreased analgesic potency of mu opioids in diabetic neuropathic pain are not fully known. The authors recently found that G protein activation stimulated by the mu opioid agonist is significantly reduced in the spinal cord dorsal horn in diabetes. In the current study, they determined potential changes in the number and binding affinity of mu opioid receptors in the spinal cord in diabetic rats. METHODS: Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The nociceptive withdrawal threshold was measured before and after intrathecal injection of morphine by applying a noxious pressure stimulus to the hind paw. The mu opioid receptor was determined with immunocytochemistry labeling and a specific mu opioid receptor radioligand, [3H]-(D-Ala2,N-Me-Phe4,Gly-ol5)-enkephalin ([3H]-DAMGO), in the dorsal spinal cord obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment. RESULTS: The antinociceptive effect of intrathecal morphine (2-10 microg) was significantly reduced in diabetic rats, with an ED50 about twofold higher than that in normal rats. However, both the dissociation constant (3.99 +/- 0.22 vs. 4.01 +/- 0.23 nm) and the maximal specific binding (352.78 +/- 37.26 vs. 346.88 +/- 35.23 fmol/mg protein) of [3H]-DAMGO spinal membrane bindings were not significantly different between normal and diabetic rats. The mu opioid receptor immunoreactivity in the spinal cord dorsal horn also was similar in normal and diabetic rats. CONCLUSIONS: The reduced analgesic effect of intrathecal morphine in diabetes is probably due to impairment of mu opioid receptor-G protein coupling rather than reduction in mu opioid receptor number in the spinal cord dorsal horn.     

Cajal间质细胞在大鼠慢传输便秘模型结肠中的变化

目的研究Cajal间质细胞（ICC）与慢传输型便秘（STC）的关系。方法用复方地芬诺酯灌胃的方法建立大鼠慢传输便秘模型（STC组）,Westernblot法测定STC组与对照组大鼠升结肠和降结肠组织ICC的特异性标志物c—kit变化情况,利用其与对应的内参B—actin灰度值的比值作为各组c—kit蛋白相对含量。结果STC组大鼠日均粪便量为（1．3±0．7）g／100g,比对照组的（1．6±0．9）g／100g明显减少,差异有统计学意义（t=10．798,P〈0．05）。STC组首粒黑粪排出时间为（461．6±150．8）min,较对照组大鼠的（351．3±119．9）min显著延长（t=2．291,P〈0．05）。STC组与对照组升结肠c—kit灰度比平均值分别为0．277±0．077和0．576±0．081（t=10．719,P〈0．05）;降结肠c—kit灰度比平均值分别为0．280±0．075和0．571±0．079（t=10．700,P〈0．05）;c．kit在STC组升结肠和降结肠的表达均下调,差异均有统计学意义。结论ICC在升结肠和降结肠的减少可能对慢传输型便秘的发生与发展有一定作用。     

Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats

To evaluate the protective role of bosentan (BOS), an endothelin‐1 (ET‐1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg^?1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg^?1 and 100 mg kg^?1, respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET‐1, eNOS, iNOS, tumour necrosis factor (TNF)‐α, ET‐RA and ET‐RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET‐1, TNF‐α and iNOS gene expressions increased, eNOS, ET‐RA and ET‐RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF‐α expressions in a dose‐dependent manner.     

Age-related decrease in aromatase and estrogen receptor （ERα and ERβ） expression in rat testes： protective effect of low caloric diets

Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）     

Pentoxifylline besides naltrexone recovers morphine‐induced inflammation in male reproductive system of rats by regulating Toll‐like receptor pathway

This study aimed to investigate the effect of pentoxifylline on complications of prolonged usage of morphine upon the testis and sperm parameters of rats. In this study, forty male Wistar rats were divided into five groups (n = 8) and treated for 56 days to only saline, only morphine, only pentoxifylline, pentoxifylline + morphine and naltrexone + morphine. The diameters of seminiferous tubules, the maturity of germ line epithelium and sperm parameters were evaluated. The expression of inflammatory‐related factors in testis tissues were also investigated at gene and protein levels. The data were calculated by one‐way ANOVA test followed by Tukey's post hoc test using SPSS software for windows (version 20). Seminiferous tubule diameter, the maturity of spermatogonia and sperm parameters were significantly decreased in morphine group in comparison with control, pentoxifylline and pentoxifylline + morphine groups (p < .001). The expression of anti‐inflammatory markers, at both gene and protein levels, was significantly increased in testis of morphine‐treated rats in comparison with other groups (p < .001). Chronic morphine administration induces destructive effects on male reproductive system by regulating inflammatory responses. Pentoxifylline recovers the destructive effects of morphine on male reproductive system by inhibiting TLR (Toll‐like receptor) activity, as an anti‐inflammatory response.     

全身炎症反应综合征患者外周血单个核细胞Toll样受体2、4基因表达及其意义

目的探讨急腹症全身炎症反应综合征(SIRS)患者外周血单个核细胞(PBMC)内Toll样受体(TLR)2、4基因表达变化及其意义。方法103例急腹症手术患者包括SIRS组65例,非SIRS组38例。采用逆转录聚合酶链反应(RT PCR)法检测TLR2、4mRNA的变化;酶联免疫吸附试验(ELISA)法检测TNF α和IL 6的表达;分析TLR2、4mRNA与TNF α和IL 6的表达量、住院时间和多器官功能障碍综合征(MODS)发生率之间的关系。结果入院第1天TLR4mRNA、TNF α和IL 6表达均升高至峰值,随后随病程下降,TLR2mRNA自入院起持续高表达至第5天,TLR2、4mRNA的表达与TNF α和IL 6、住院时间呈正相关,且TLR2、4mRNA表达越高,发生MODS的危险性越大。结论急腹症SIRS患者PBMC内TLR2、4基因表达显著增加,提示TLR在急腹症SIRS的发生发展过程中发挥了重要的促进作用。