东南大学学报(医学版)
東南大學學報(醫學版)
동남대학학보(의학판)
JOURNAL OF SOUTHEAST UNIVERSITY(MEDICAL SCIENCE EDITION)
2013年
5期
538-542
,共5页
陈骏毅%周全博%张岷%陈炜%罗蒙
陳駿毅%週全博%張岷%陳煒%囉矇
진준의%주전박%장민%진위%라몽
门静脉高压%高动力循环%钙调蛋白
門靜脈高壓%高動力循環%鈣調蛋白
문정맥고압%고동력순배%개조단백
portal hypertension%hyperdynamic circulation%calmodulin
目的:检测钙调蛋白(calmodulin,CaM)在肝硬化门静脉高压(portal hypertension,PHT)的大鼠内脏动脉中的表达变化,探讨其在肝硬化PHT高动力循环中的作用及可能的机制。方法:检测并比较对照组( n=8)和四氯化碳(CCl4)诱导的肝硬化PHT组(n=8)大鼠的门静脉血流量、门静脉压力、离体肠系膜微动脉对去甲肾上腺素( norepinephrine ,NE)的反应性,CaM特异性抑制剂W-7对离体肠系膜微动脉收缩反应性、各组大鼠肠系膜动脉CaM和磷酸化内皮型一氧化氮合酶( phosphorylation of endothelial nitric oxide synthase , p-eNOS)的蛋白表达变化的影响。结果:(1) PHT组门静脉血流量明显低于对照组,W-7对PHT组门静脉血流量无明显改善作用;(2) PHT组门静脉压力明显高于对照组,W-7对PHT组门静脉压力亦无明显降低作用;(3) PHT组肠系膜微动脉对NE的收缩反应性明显降低,EC50明显增大,W-7能部分改善这种低反应性;(4) PHT组肠系膜动脉内CaM和p-eNOS的蛋白水平较对照组明显升高,W-7能明显降低PHT组肠系膜动脉内p-eNOS的蛋白表达。结论:CCl4诱导肝硬化PHT大鼠肠系膜动脉中过度生成的CaM可能通过参与或协同生成p-eNOS等方式来促进eNOS的活性增加,最终促进一氧化氮(nitric oxide,NO)的生物合成,降低肠系膜微动脉对NE的反应性,并引起内脏血管扩张,参与内脏高动力循环的形成。
目的:檢測鈣調蛋白(calmodulin,CaM)在肝硬化門靜脈高壓(portal hypertension,PHT)的大鼠內髒動脈中的錶達變化,探討其在肝硬化PHT高動力循環中的作用及可能的機製。方法:檢測併比較對照組( n=8)和四氯化碳(CCl4)誘導的肝硬化PHT組(n=8)大鼠的門靜脈血流量、門靜脈壓力、離體腸繫膜微動脈對去甲腎上腺素( norepinephrine ,NE)的反應性,CaM特異性抑製劑W-7對離體腸繫膜微動脈收縮反應性、各組大鼠腸繫膜動脈CaM和燐痠化內皮型一氧化氮閤酶( phosphorylation of endothelial nitric oxide synthase , p-eNOS)的蛋白錶達變化的影響。結果:(1) PHT組門靜脈血流量明顯低于對照組,W-7對PHT組門靜脈血流量無明顯改善作用;(2) PHT組門靜脈壓力明顯高于對照組,W-7對PHT組門靜脈壓力亦無明顯降低作用;(3) PHT組腸繫膜微動脈對NE的收縮反應性明顯降低,EC50明顯增大,W-7能部分改善這種低反應性;(4) PHT組腸繫膜動脈內CaM和p-eNOS的蛋白水平較對照組明顯升高,W-7能明顯降低PHT組腸繫膜動脈內p-eNOS的蛋白錶達。結論:CCl4誘導肝硬化PHT大鼠腸繫膜動脈中過度生成的CaM可能通過參與或協同生成p-eNOS等方式來促進eNOS的活性增加,最終促進一氧化氮(nitric oxide,NO)的生物閤成,降低腸繫膜微動脈對NE的反應性,併引起內髒血管擴張,參與內髒高動力循環的形成。
목적:검측개조단백(calmodulin,CaM)재간경화문정맥고압(portal hypertension,PHT)적대서내장동맥중적표체변화,탐토기재간경화PHT고동력순배중적작용급가능적궤제。방법:검측병비교대조조( n=8)화사록화탄(CCl4)유도적간경화PHT조(n=8)대서적문정맥혈류량、문정맥압력、리체장계막미동맥대거갑신상선소( norepinephrine ,NE)적반응성,CaM특이성억제제W-7대리체장계막미동맥수축반응성、각조대서장계막동맥CaM화린산화내피형일양화담합매( phosphorylation of endothelial nitric oxide synthase , p-eNOS)적단백표체변화적영향。결과:(1) PHT조문정맥혈류량명현저우대조조,W-7대PHT조문정맥혈류량무명현개선작용;(2) PHT조문정맥압력명현고우대조조,W-7대PHT조문정맥압력역무명현강저작용;(3) PHT조장계막미동맥대NE적수축반응성명현강저,EC50명현증대,W-7능부분개선저충저반응성;(4) PHT조장계막동맥내CaM화p-eNOS적단백수평교대조조명현승고,W-7능명현강저PHT조장계막동맥내p-eNOS적단백표체。결론:CCl4유도간경화PHT대서장계막동맥중과도생성적CaM가능통과삼여혹협동생성p-eNOS등방식래촉진eNOS적활성증가,최종촉진일양화담(nitric oxide,NO)적생물합성,강저장계막미동맥대NE적반응성,병인기내장혈관확장,삼여내장고동력순배적형성。
Objective: To detect the variation of calmodulin ( CaM ) in the splanchnic arteries under portal hypertension ( PHT) , and investigate its effect on the hyperdynamic circulation of PHT and its possible mechanism . Method: Portal vein blood flow , portal vein pressure , the reaction of mesenteric microcirculation artery to norepinephrine (NE) were detected and compared between the control group (n=8) and PHT group (the rats with the liver cirrhosis caused by CCl4,n=8).The influence of the specific inhibitor of CaM-W-7 on the contractile response of isolated mesenteric microcirculation artery and the protein expression of CaM and phosphorylation of endothelial nitric oxide synthase ( p-eNOS) in mesentery artery were observed .Results:(1) Portal vein blood flow of PHT group was apparently lower than that of control group ,W-7 had no significant effect on portal vein blood flow of PHT group.(2) Portal vein pressure of PHT group was much higher than that of control group ,W-7 had little influence on reducing portal vein pressure of PHT group either .( 3 ) The contractile response of mesenteric microcirculation artery to NE in PHT group was decreased significantly , EC50 increases significantly , W-7 could improve this kind of hypoergia partially .(4) Compared with control group , the protein expression of CaM and p-eNOS in mesentery artery of PHT group increased quite a lot , W-7 could decrease the protein expression of p-eNOS significantly .Conclusion:The overproduced CaM in the mesenteric artery of the PHT rats may activate the eNOS by participating in or cooperating with the producing of p-eNOS, then enhance the synthesis of nitric oxide ( NO) , reduce the contractile response to norepinephrine of mesenteric microcirculation artery , cause the splanchnic vasodilatation , involve in the formation of splanchnic hyperdynamic circulation .