CAJ | 학술논문

目的探讨血红素氧合酶(HO)阻滞剂锌原卟啉(ZnPP)对糖尿病(DM)大鼠结肠动力和Cajal间质细胞(ICC)的影响.方法雄性SD大鼠腹腔注射链脲佐菌素(STZ),3 d后选取成功造模大鼠24只作为DM组,另取正常大鼠16只作为对照组.饲养6周时,选取DM组大鼠和对照组大鼠各8只,行碳末推进实验,确认有无胃肠动力障碍.剩余DM组大鼠第6周起予以干预,DM未干预组(8只)0.1 mol/L磷酸盐缓冲液腹腔注射,隔日1次,连续3周;DM+ZnPP组(8只),ZnPP 10 μmol/kg腹腔注射,隔日1次,连续3周.对照组(8只)予以膜腔注射0.1 mmol/L磷酸盐缓冲液.Western印迹法检测结肠组织HO-1、HO-2和c-kit表达.免疫组化法测定结肠组织HO-1、HO-2和c-kit阳性细胞面积.结果 DM未干预组胃肠推进指数为(63.0±1.2)%,较对照组显著减低[(71.85:2.0)%,P<0.05];而DM+ZnPP组胃肠推进指数为(72.5±2.6)%,较DM未干预组明显改善(P<0.05),且与对照组差异无统计学意义(P>0.05).DM+ZnPP组近、远端结肠HO-1表达明显下降(P<0.05).DM未干预组和DM+ZnPP组近端结肠HO-2表达均较对照组显著减少(P<0.05).DM未干预组近、远端结肠组织c-kit较对照组显著减少(P<0.05);DM+ZnPP组c-kit的表达较DM未干预组明显改善(P<0.05),且与对照组间差异无统计学意义(P>0.05).结论 ZnPP可能通过阻滞HO-1对DM大鼠结肠Cajal间质细胞有保护作用,并改善其结肠动力障碍.
목적 탐토혈홍소양합매(HO)조체제자원계람(ZnPP)대당뇨병(DM)대서결장동력화Cajal간질세포(ICC)적영향.방법 웅성SD대서복강주사련뇨좌균소(STZ),3 d후선취성공조모대서24지작위DM조,령취정상대서16지작위대조조.사양6주시,선취DM조대서화대조조대서각8지,행탄말추진실험,학인유무위장동력장애.잉여DM조대서제6주기여이간예,DM미간예조(8지)0.1 mol/L린산염완충액복강주사,격일1차,련속3주;DM+ZnPP조(8지),ZnPP 10 μmol/kg복강주사,격일1차,련속3주.대조조(8지)여이막강주사0.1 mmol/L린산염완충액.Western인적법검측결장조직HO-1、HO-2화c-kit표체.면역조화법측정결장조직HO-1、HO-2화c-kit양성세포면적.결과 DM미간예조위장추진지수위(63.0±1.2)%,교대조조현저감저[(71.85:2.0)%,P<0.05];이DM+ZnPP조위장추진지수위(72.5±2.6)%,교DM미간예조명현개선(P<0.05),차여대조조차이무통계학의의(P>0.05).DM+ZnPP조근、원단결장HO-1표체명현하강(P<0.05).DM미간예조화DM+ZnPP조근단결장HO-2표체균교대조조현저감소(P<0.05).DM미간예조근、원단결장조직c-kit교대조조현저감소(P<0.05);DM+ZnPP조c-kit적표체교DM미간예조명현개선(P<0.05),차여대조조간차이무통계학의의(P>0.05).결론 ZnPP가능통과조체HO-1대DM대서결장Cajal간질세포유보호작용,병개선기결장동력장애.
Objective To assess the effects of zinc protoporphyrin (ZnPP), an inhibitor of the heme oxygenase (HO), on the colonic interstitial cells of Cajal (ICC) of diabetic rats with colonic slow transit. Methods Diabetes mellitus (DM) model was induced by intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. Twenty four successfully established DM rats were selected, and 16 healthy rats were served as controls. Six weeks later, gastrointestional (GI) dysfunction was observed by charcoal propulsion experiment in 8 DM rats and 8 controls. The rest rats in DM group were divided into 2 groups: DM rats intraperitoneal injected with PBS (n=8) or with 10 μmol/kg of ZnPP (n = 8) every other day for 3 weeks. The rats in control group (n = 8) were intraperitoneally injected with PBS. The levels of HO and c-kit (the special receptor of ICC) expression were detected by Western blotting. The distribution of ICC was observed by immunohistochemistry and the area of c-kit positive cells was counted. Results The GI propulsion rate in DM rats interfered with PBS was significantly declined compared to that in the controls (63.0%± 1.2% vs 71.8%±2.0%, P<0.05). But it was improved in DM rats interfered with ZnPP (72.5± 2.6%, P<0.05), which showed no significant differentee with that in control group (P>0.05). The expression of HO-1 in close and distant colon of DM rats interfered with ZnPP was decreased (P< 0.05). The expression of HO-2 in close colon and the area of c-kit positive cells of DM rats interfered with PBS was reduced compared with that in controls (P<0.05), but both were improved in DM rats interfered with ZnPP (P<0. 05). Conclusion Administration of ZnPP might be able to protect ICC by its blockage of HO-1 in DM rats with gastrointestinal dysfunction.