摘要
目的 探讨D4受体在MPTP诱导的胃肠道黏膜损害中的作用。方法 SD大鼠随机分为 8组 (每组 5～ 9只 ) :生理盐水组 ;喹吡罗 0 5mg/kg及 1mg/kg组 ;氯氮平组 ;喹吡罗 0 5mg/kg +MPTP组 ;喹吡罗 1 0mg/kg +MPTP组 ;氯氮平 +MPTP组 ;MPTP组。分别给药后 ,测量胃、十二指肠黏膜损伤指数 ;留取黏膜检测NO和一氧化氮合酶 (iNOS)。结果 ( 1)MPTP腹腔注射可造成胃、十二指肠黏膜明显损伤 ,损伤指数较对照组高 5～ 6倍 (P <0 0 1)。 ( 2 )单独使用喹吡罗或氯氮平对黏膜无影响 ;喹吡罗可明显减轻MPTP造成的大鼠胃、十二指肠黏膜损伤 (P <0 0 5 ) ,并呈量效关系 ;氯氮平对MPTP大鼠的黏膜损伤无明显影响。 ( 3)MPTP组胃、十二指肠黏膜NO含量和iNOS活性较对照为低 ,十二指肠更为明显 (P <0 0 5 ) ;NO的含量和iNOS活性与损伤指数呈负相关 (NO :r=- 1 0 ,P <0 0 0 1;iNOS :r=- 0 0 6 2 4 ,P =0 0 2 1)。结论 MPTP可导致大鼠胃、十二指肠黏膜明显损伤 ,部分是通过降低黏膜iNOS活性和NO水平而起作用。D4的激动剂喹吡罗能够拮抗MPTP诱导的胃肠黏膜损伤 ;
Objective Using the dopamine 4 receptor (D 4) agonist quinpirole (Q ) and antagonist clozapine (C ) to investigate the role of D 4 in MPTP induced gastrointestinal injury in rat Methods SD rats were randomly divided into 8 groups( n =5～9 each group): NS as control; Q 0 5 mg/kg; Q 1 mg/kg; C 10 mg/kg; Q 0 5 mg/kg+MPTP; Q 1 mg/kg+MPTP; and MPTP l mg/100 g After treated with the differentchemicals, the gastric and duodenal mucosa lesion index (LI) was recorded Gastric and duodenal mucosa was collected to assay NO and iNOS by spectrophotometer Results (1) MPTP peritoneal injection induced significant gastro duodenal mucosa injury; both gastric and duodenal LI were 5～6 fold higher than control group ( P <0 01) (2) Q or C used alone showed no effect on gastro duodenal mucosa, Q used before MPTP could resist the MPTP induced mucosa injury, especially in duodenum ( P <0 01) This effectiveness is dose dependent C had no effect on gastro duodenal mocosa protection (3) The mucosal NO concentration and iNOS activity in MPTP group were lower than that in control, especially in duodenum ( P <0 05) They were negative correlated with LI Conclusion MPTP peritoneal injection induced significant gastro duodenal mucosa injury in rat, mediated partially by decreasing the activity of mucosa iNOS and NO concentration D 4 agonist Q could resist the effectiveness of MPTP induced mucosa injury, while the antagonist C had no effect
出处
《中华医学杂志》
CAS
CSCD
北大核心
2003年第18期1611-1614,共4页
National Medical Journal of China
基金
国家自然科学青年基金资助项目 (3 980 0 0 66)
