兰州大学机构库 >生命科学学院
I型糖尿病改变了内吗啡肽对小鼠结肠收缩特性的影响
Alternative TitleType 1 diabetes alters the modulatory effects of endomorphins on mouse colonic motility
郭超
Thesis Advisor王锐
2009-05-27
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword内吗啡肽 四氧嘧啶 I型糖尿病 消化系统
Abstract通过建立由四氧嘧啶诱导的I型糖尿病小鼠模型,离体和在体条件下研究了内吗啡肽(EMs)对糖尿病小鼠消化系统的影响。在建立糖尿病小鼠模型4周之后,碳酰胆碱引起的末端结肠纵形肌的收缩反应与非糖尿病小鼠相比明显减弱。此外,EMs引起的末端结肠纵形肌和近端结肠环形肌的收缩反应明显的受到I型糖尿病的影响而削弱。EMs引起的末端结肠纵形肌的收缩没有受到阿托品、L-NAME、酚妥拉明、普萘洛尔、六烃己胺、二甲麦角新碱、纳曲吲哚的影响。另一方面,河鲀毒素,吲哚美辛,纳洛酮,β-funaltrexamine,纳洛肼,nor-BNI完全消除了EMs引起的末端结肠纵形肌的收缩作用,表明在糖尿病小鼠和非糖尿病小鼠中EMs发挥以上调节作用的机制是相似的。在建立糖尿病小鼠模型8周之后,碳酰胆碱和EMs诱导的纵形肌的收缩情况与建立糖尿病模型四周之后的小鼠相似。所有的结果都表明I型糖尿病会显著削弱EMs引起的离体小鼠结肠收缩反应,但是介导这一作用的机制并没有发生改变。 在体对比研究了正常状态下和I型糖尿病状态下,侧脑室(i.c.v.)注射EMs对小鼠肠道运动功能的影响。在正常小鼠中,EM1和EM2都能剂量依赖的增加结肠排珠时间和减小凝胶在大肠中移动的距离。EM1和EM2对4周糖尿病小鼠结肠排珠的抑制比正常小鼠进一步加强。在8周糖尿病小鼠中,低浓度的EM1(0.5nmoL,1.5nmoL)对结肠排珠的抑制要比正常小鼠和4周糖尿病小鼠弱。但高浓度的EM1(5nmoL)的抑制作用比正常小鼠高,而比4周糖尿病小鼠弱。EM1和EM2对4周糖尿病小鼠大肠排凝胶的抑制比正常小鼠进一步加强。在8周糖尿病小鼠中,EM1和EM2对结肠排凝胶的抑制比正常小鼠强,而比4周糖尿病小鼠弱。总之,在体结果表明,I型糖尿病改变了介导i.c.v.EMs诱导的肠道功能效应变化的阿片系统。纳洛酮共同注射可显著的拮抗EMs上述作用,表明和正常小鼠一样,介导这一作用的机制并没有发生改变。
Other AbstractEndomorphins, the endogenous, potent and sective μ-opioid receptor agonists, have been shown to induce longitudinal muscle contactions of distal colon in mice. In the present study, to assess whether diabetes alters these modulatory effects of EMs on colonic motility, we investigated the effects of EMs in type 1 diabetic mouse colon in vitro. At 4 weeks after the onset of diabetes, carbachol-induced contractions in the longitudinal muscle of distal colon were significantly reduced compared to those of non-diabetic mice. Furthermore, the contractile effects induced by EMs in the longitudinal muscle of distal colon and in the circular muscle of proximal colon were also significantly reduced by type 1 diabetes. It is noteworthy that EMs-induced longitudinal muscle contractions were not significantly affected by atropine, Nω-nitro-L-arginine methylester(L-NAME),phentolamine,propranolol, hexamethonium,methysergide and naltrindole. On the other hand, tetrodotoxin, indomethacin, naloxone, β-funaltrexamine, naloxonazine and norbinaltorphimine completely abolished these effects. These mechanisms responsible for EMs-induced modulatory effects in type 1 diabetes were in good agreement with those of non-diabetes, indicating similar mechanisms in both diabetes and non-diabetes. At 8 weeks after the onset of diabetes, both carbachol- and EMs-induced longitudinal muscle contractions were similar to those of short-time (4weeks) diabetic mice. In summary, all the results indicated that type 1 diabetes significantly attenuated the modulatory effects of EMs on the mouse colonic motility, but the mechanisms responsible for these effects were not significantly altered. We compared the effects of i.c.v.EMs on gastrointestinal functions in normal mice and diabetic mice in vivo.When given centrally, both EM1 and EM2 can dose-dependent inhibite colonic bead expulsion and retarde the rate of large intestinal transit in normal mice in a naloxone-sensitive manner. Compared to those of normal mice, EMs induced inhibition of colonic bead expulsion in diabetic mice was further enhanced. EM1 at low concentrations(0.5nmoL , 1.5nmoL) induced inhibition of colonic bead expulsion in 8 weeks diabetic mice was weaker than that in normal mice and 4 weeks diabetic mice. EM1 at high concentration (5nmoL) induced inhibition of colonic bead expulsion was weaker than in normal mice ,but higher than in 4 weeks diabe...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221957
Collection生命科学学院
Recommended Citation
GB/T 7714
郭超. I型糖尿病改变了内吗啡肽对小鼠结肠收缩特性的影响[D]. 兰州. 兰州大学,2009.
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