中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2015年
4期
725-731
,共7页
刘颖%全晓静%夏虹%罗和生
劉穎%全曉靜%夏虹%囉和生
류영%전효정%하홍%라화생
慢性应激%高动力%硫化氢%ATP敏感性钾通道
慢性應激%高動力%硫化氫%ATP敏感性鉀通道
만성응격%고동력%류화경%ATP민감성갑통도
Chronic stress%Hypermotility%Hydrogen sulfide%ATP-sensitive potassium channels
目的：研究外源性硫化氢（ hydrogen sulfide，H2 S）及ATP敏感性钾通道（ ATP-sensitive potassium channels，KATP）在慢性应激结肠高动力中的作用。方法：制作慢性避水应激（water avoidance stress，WAS）和假避水应激（ sham water avoidance stress，SWAS）大鼠模型，观察2组大鼠结肠肌条的收缩活性以及硫氢化钠（ NaHS）和格列本脲预处理后对2组大鼠结肠肌条收缩影响并计算NaHS的半数抑制浓度（ half maximal inhibitory concentration， IC50），使用免疫荧光及Western blotting法观察KATP通道各亚基在结肠中的分布及表达。结果：WAS组结肠肌条收缩活性明显高于SWAS组；NaHS浓度依赖性抑制2组大鼠纵行肌（ longitudinal muscle，LM）和环形肌（ circular mus-cle，CM）的收缩；WAS组LM和CM的NaHS IC50分别为0.2033 mmol／L和0.1438 mmol／L，均明显低于SWAS组（P＜0.01）；格列本脲明显增加2组大鼠肌条NaHS IC50（P＜0.01）；Kir6.1、Kir6.2和SUR-2B在2组大鼠结肠固有肌细胞膜均有分布；WAS组（去除黏膜及黏膜下层后）Kir6.1和SUR2B蛋白表达高于SWAS组（P＜0.01）。结论：H2 S外源性供体NaHS对慢性应激结肠高动力具有潜在的治疗作用。 KATP通道亚基Kir6.1／SUR2B表达增加可能是慢性应激结肠动力紊乱的一种适应性反应。
目的：研究外源性硫化氫（ hydrogen sulfide，H2 S）及ATP敏感性鉀通道（ ATP-sensitive potassium channels，KATP）在慢性應激結腸高動力中的作用。方法：製作慢性避水應激（water avoidance stress，WAS）和假避水應激（ sham water avoidance stress，SWAS）大鼠模型，觀察2組大鼠結腸肌條的收縮活性以及硫氫化鈉（ NaHS）和格列本脲預處理後對2組大鼠結腸肌條收縮影響併計算NaHS的半數抑製濃度（ half maximal inhibitory concentration， IC50），使用免疫熒光及Western blotting法觀察KATP通道各亞基在結腸中的分佈及錶達。結果：WAS組結腸肌條收縮活性明顯高于SWAS組；NaHS濃度依賴性抑製2組大鼠縱行肌（ longitudinal muscle，LM）和環形肌（ circular mus-cle，CM）的收縮；WAS組LM和CM的NaHS IC50分彆為0.2033 mmol／L和0.1438 mmol／L，均明顯低于SWAS組（P＜0.01）；格列本脲明顯增加2組大鼠肌條NaHS IC50（P＜0.01）；Kir6.1、Kir6.2和SUR-2B在2組大鼠結腸固有肌細胞膜均有分佈；WAS組（去除黏膜及黏膜下層後）Kir6.1和SUR2B蛋白錶達高于SWAS組（P＜0.01）。結論：H2 S外源性供體NaHS對慢性應激結腸高動力具有潛在的治療作用。 KATP通道亞基Kir6.1／SUR2B錶達增加可能是慢性應激結腸動力紊亂的一種適應性反應。
목적：연구외원성류화경（ hydrogen sulfide，H2 S）급ATP민감성갑통도（ ATP-sensitive potassium channels，KATP）재만성응격결장고동력중적작용。방법：제작만성피수응격（water avoidance stress，WAS）화가피수응격（ sham water avoidance stress，SWAS）대서모형，관찰2조대서결장기조적수축활성이급류경화납（ NaHS）화격렬본뇨예처리후대2조대서결장기조수축영향병계산NaHS적반수억제농도（ half maximal inhibitory concentration， IC50），사용면역형광급Western blotting법관찰KATP통도각아기재결장중적분포급표체。결과：WAS조결장기조수축활성명현고우SWAS조；NaHS농도의뢰성억제2조대서종행기（ longitudinal muscle，LM）화배형기（ circular mus-cle，CM）적수축；WAS조LM화CM적NaHS IC50분별위0.2033 mmol／L화0.1438 mmol／L，균명현저우SWAS조（P＜0.01）；격렬본뇨명현증가2조대서기조NaHS IC50（P＜0.01）；Kir6.1、Kir6.2화SUR-2B재2조대서결장고유기세포막균유분포；WAS조（거제점막급점막하층후）Kir6.1화SUR2B단백표체고우SWAS조（P＜0.01）。결론：H2 S외원성공체NaHS대만성응격결장고동력구유잠재적치료작용。 KATP통도아기Kir6.1／SUR2B표체증가가능시만성응격결장동력문란적일충괄응성반응。
[ ABSTRACT] AIM:To investigate the potential role of exogenous hydrogen sulfide ( H2 S) and ATP-sensitive po-tassium ( KATP ) channels in chronic stress-induced colonic hypermotility.METHODS:Male Wistar rats were divided into water avoidance stress ( WAS) group and sham WAS ( SWAS) group.Organ bath recordings were used to test the contrac-tile activity of colonic strips.The effects of H2 S donor NaHS and pretreatment with glibenclamide on the contractions of co-lonic smooth muscle were studied and the IC50 of NaHS was calculated.The localization and expression of the subunits of KATP channels were determined by the methods of immunohistochemistry and Western blotting.RESULTS:WAS increased contractile activity of colonic strips.NaHS concentration-dependently inhibited the spontaneous contractions of strips from the SWAS and WAS rats.The IC50 of NaHS for longitudinal muscle ( LM) and circular muscle ( CM) of the WAS rats was 0.2033 mmol/L and 0.1438 mmol/L, significantly lower than those of the SWAS rats.Glibenclamide significantly in-creased the IC50 of NaHS for LM and CM from the SWAS and WAS rats.In both SWAS and WAS rat colon, Kir6.1, Kir6.2 and SUR2B were expressed on the plasma membrane of the smooth muscle cells.WAS treatment resulted in up-reg-ulation of the expression of Kir6.1 and SUR2B in the colon devoid of mucosa and submucosa.CONCLUSION: The in-creased expression of Kir 6.1 and SUR2B in colonic smooth muscle cells may be a defensive response to chronic WAS.H2 S donors may have potential clinical effect on treating chronic stress-induced colonic hypermotility.
