Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats
Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats
复制标题
利钠肽依赖性 cGMP 信号通路增强链脲佐菌素诱导的糖尿病大鼠胃平滑肌的松弛
DOI：
10.1007/s10620-009-0766-8
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Xu, Wen-Xie
中科院分区：
文献类型：
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作者：
Xu, Dong-Yuan;Liu, Lan;Xu, Wen-Xie
糖尿病常见的胃肠道并发症是胃轻瘫，胃轻瘫患者可能出现早饱、恶心、呕吐、腹胀、餐后饱胀或上腹痛。但其发病机制尚不清楚。最近的研究表明，心房钠尿肽（ANP）由胃粘膜分泌，其家族在胃肠运动的调节中起抑制作用，但关于ANP信号通路在糖尿病胃轻瘫中的作用尚未见报道。本研究探讨C型利钠肽（CNP）颗粒鸟苷酸环化酶（pGC）环磷酸鸟苷（cGMP）信号通路对链脲佐菌素（STZ）诱导的糖尿病大鼠胃轻瘫的影响。将雄性SD大鼠分为两组，I组为正常对照组，II组为STZ诱导的糖尿病大鼠，诱导4周后进行实验。用生理记录仪记录正常和糖尿病大鼠胃平滑肌条的自发收缩。用放射免疫分析法（RIA）测定了正常和糖尿病大鼠胃平滑肌对CNP和cGMP产生的反应性pGC活性。CNP对STZ诱导的糖尿病大鼠胃窦环行平滑肌条有较长的舒张作用。CNP对自发收缩的抑制作用呈剂量依赖性，糖尿病大鼠的抑制百分率分别为25.5 +/-A1.7%，43.6 +/-A3.2%，85.1 +/-A2.5%，20.5 +/-A1.5%，31.1 +/-A1.7%，对照组在0.01、0.03和0.1 μ mol/l浓度下分别为58.9 +/- A 3.7%。在STZ诱导的糖尿病大鼠中，CNP反应的胃肌肉组织中的cGMP产生和pGC活性显着增强。正常和糖尿病大鼠胃平滑肌均表达B型利钠肽受体（NPR-B）基因，糖尿病大鼠表达增强。结果表明，利钠肽依赖的pGC-cGMP信号上调，可能有助于STZ诱导的糖尿病大鼠的糖尿病胃轻瘫。
A common gastrointestinal complication of diabetes is gastroparesis, and patients with gastroparesis may present with early satiety, nausea, vomiting, bloating, postprandial fullness, or upper abdominal pain. However, the pathogenesis is not clear yet. A recent study indicated that atrial natriuretic peptide (ANP) was secreted from the gastric mucosa and the ANP family plays an inhibitory role in the regulation of gastrointestinal motility, but the effect of the natriuretic peptide signal pathway on diabetic gastroparesis has not been reported. The study investigated the effect of C-type natriuretic peptide (CNP) particulate guanylyl cyclase (pGC) cyclic guanosine monophosphate (cGMP) signaling on gastroparesis in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into two groups; group I: normal control rats; group II: STZ-induced diabetic rats; 4 weeks after induction, the experiments were performed. The spontaneous contraction of gastric smooth muscle strips was recorded by using physiographs in control and diabetic rats. The pGC activity in response to CNP and cGMP production in gastric smooth muscle were measured by using radioimmunoassay (RIA) in normal and diabetic rats. CNP induced a longer lasting relaxation of gastric antral circular smooth muscle strips in STZ-induced diabetic rats. The inhibitory effect of CNP on spontaneous contraction revealed a dose-dependency, and the inhibitory percentages were 25.5 +/- A 1.7%, 43.6 +/- A 3.2%, 85.1 +/- A 2.5% in diabetic rats and 20.5 +/- A 1.5%, 31.1 +/- A 1.7%, 58.9 +/- A 3.7% in the control group at the concentrations of 0.01, 0.03, and 0.1 mu mol/l, respectively. The cGMP production and pGC activity in response to CNP in gastric muscle tissues were significantly potentiated in STZ-induced diabetic rats. Natriuretic peptide receptor type B (NPR-B) gene was expressed in the gastric smooth muscles of normal and diabetic rats, and the expression was increased in diabetic rats. The results suggest that natriuretic peptide-dependent pGC-cGMP signal is upregulated and may contribute to diabetic gastroparesis in STZ-induced diabetic rats.