墨蝶呤对糖尿病胃轻瘫大鼠胃排空影响及其机制

EFFECTS AND MECHANISMS OF SEPIAPTERIN ON GASTRIC EMPTYING IN DIABETIC RATS WITH GASTROPARESIS

目的观察链脲佐菌素(STZ)所致糖尿病大鼠胃运动改变,探讨墨蝶呤(SEP)对雌性糖尿病大鼠胃排空的影响及机制。方法采用腹腔注射STZ诱导糖尿病大鼠模型。将大鼠分为6组,观察血糖、体质量、胃排空率,采用电场刺激测定胃平滑肌条舒张反应,应用Western blot法检测胃一氧化氮合酶(nNOS)蛋白表达。结果与正常大鼠相比较,糖尿病大鼠体质量明显下降(F=4.16,q=3.27,P<0.01),血糖明显升高(F=59.48,q=12.91,P<0.01),胃排空率显著降低(F=25.59,q=10.80,P<0.01);给予SEP灌胃后,糖尿病大鼠胃排空率显著升高(q=8.68,P<0.01)。与正常大鼠相比较,电刺激平滑肌条可使糖尿病大鼠胃平滑肌条舒张作用明显减弱(F=40.17,q=12.52,P<0.01);给予SEP灌胃后,电刺激平滑肌条可使糖尿病大鼠胃平滑肌条舒张作用显著增强(q=7.33,P<0.01)。糖尿病大鼠胃组织nNOS蛋白表达水平较正常大鼠显著降低(F=13.32,q=6.96,P<0.01);给予SEP灌胃后,大鼠nNOS蛋白表达水平显著升高,接近正常水平(q=7.34,P<0.01)。结论 SEP可加速糖尿病大鼠胃排空,并增加胃nNOS蛋白表达。对于女性糖尿病胃轻瘫病人,SEP治疗可能为一种有效的治疗方法。

Objective To observe the changes of gastric motility in diabetic rats induced by streptozotoein （STZ） and in- vestigate the influence and mechanism of sepiapterin （SEP） on gastric emptying in female diabetic rats. Methods A diabetic model was created in female rats by intraperitoneal injection of STZ. The rats were divided into six groups. Blood glucose, body weight, and gastric emptying rate were detected. The relaxation of gastric musclar strips was measured by electrical stimulation and the expression of nNOS was detected by Western blot. Results Compared with the normal rats： the body weight in the diabetic rats declined （F 4.16,q=3.27,P〈0.01）, bloodsugar elevated （F=59.48,q=12.91,P〈0.01）, and gastric emptying lowered （F=25.59,q= 10.80,P〈0.01）, the emptying rate increased after intragastric administration of SEP （q=8.68,P〈0.01） ; electri- cal stimulation of muscular strips could significantly diminish the relaxation of smooth muscular trips in the rats （F = 40.17, q- 12.52,P〈0.01）, the muscle-strip relaxation became strong at electrical stimulation after intragastrie SEP （q = 7.33, P〈 0.01）. The expression of nNOS protein in diabetic rats was lower than that in the normal rats （F=13.32, q = 6.96, P 〈0.01）, after intra- gastric SEP, the nNOS protein expression markedly increased, approaching its normal level （q=7.34,P〈0.01）. Conclusion SEP can accelerate gastric emptying and increase the nNOS protein expression in diabetic rats. For women with diabetes, SEP might become an effective therapy.