中华临床营养杂志
中華臨床營養雜誌
중화림상영양잡지
CHINESE JOURNAL OF CLINICAL NUTRITION
2013年
4期
218-224
,共7页
刘业成%何桂珍%齐志伟%徐军%朱华栋%王仲%于学忠%马遂
劉業成%何桂珍%齊誌偉%徐軍%硃華棟%王仲%于學忠%馬遂
류업성%하계진%제지위%서군%주화동%왕중%우학충%마수
应激%促肾上腺激素释放激素%脑梗死%胃肠屏障
應激%促腎上腺激素釋放激素%腦梗死%胃腸屏障
응격%촉신상선격소석방격소%뇌경사%위장병장
Stress%Corticotrophin-releasing hormone%Cerebral infarction%Gastrointestinal barrier
目的 探讨促肾上腺激素释放激素(CRH)在脑梗死胃肠屏障破坏中的作用.方法 雄性Wistar大鼠40只,按随机数字表法分为假手术组(C组)、脑梗死组(Ⅰ组)、脑梗死+脑室α-螺旋-CRH (9-41)组(Aic组)、脑梗死+腹腔α-螺旋-CRH (9-41)组(Aip组),每组10只.造模成功后留24 h尿检测尿肾上腺素、去甲肾上腺素、皮质醇含量及蔗糖排出率,造模后24 h检测血浆二胺氧化酶(DAO)活性和D-乳酸浓度；进行胃大体Guth评分,Western-blot法检测下丘脑组织的CRH蛋白表达.结果 各组24h尿肾上腺素、去甲肾上腺素、24 h皮质醇含量和下丘脑组织的CRH蛋白表达变化趋势一致:与C组比较,Ⅰ组显著升高[24h尿肾上腺素(42.28±19.86)比(13.11±7.56) ng (P=0.039),去甲肾上腺素(265.96±82.09)比(156.65±60.28) ng (P =0.042),24 h皮质醇含量(239.85±73.85)比(106.13±47.47) ng (P =0.006),下丘脑组织的CRH蛋白表达1.36±0.42比0.59±0.27 (P=0.002)],Aip组亦显著升高[24h尿肾上腺素(77.89±34.17)比(13.11±7.56) ng (P=0.009),去甲肾上腺素(380.49±97.00)比(156.65±60.28) ng (P=0.007),24 h皮质醇含量(276.13±99.24)比(106.13±47.47) ng (P =0.007),下丘脑组织CRH蛋白表达1.18 ±0.26比0.59±0.27 (P =0.003)],Aic组差异无统计学意义；Ⅰ组显著高于Aic组[24 h尿肾上腺素(42.28±19.86)比(17.93±6.25) ng (P =0.036),去甲肾上腺素(265.96±82.09)比(160.50±34.88) ng (P=0.038),24h皮质醇含量(239.85±73.85)比(127.90±47.17) ng(P =0.005),下丘脑组织CRH蛋白表达1.36±0.42比0.82±0.20 (P =0.027)],Aip组也显著高于Aic组[24h尿肾上腺素(77.89±34.17)比(17.93±6.25) ng (P=0.008),去甲肾上腺素(380.49 ±97.00)比(160.50±34.88) ng (P=0.007),24 h皮质醇含量(276.13±99.24)比(127.90±47.17) ng (P=0.004),CRH蛋白表达1.18±0.26比0.82±0.20 (P =0.039)].各组尿蔗糖排出率、胃大体评分变化趋势一致:与C组比较,Ⅰ组显著升高[尿蔗糖排出率(2.19±0.88)％比(0.54±0.29)％(P=0.005),胃大体评分(13.90±5.28)比(1.50±1.43)分(P=0.003)]；Aip组亦显著升高[尿蔗糖排出率(2.00±0.63)％比(0.54±0.29)％ (P =0.007),胃大体评分(9.90±6.60)比(1.50±1.43)分(P =0.005)]；Aic组显著低于Ⅰ组[尿蔗糖排出率(0.82±0.36)％比(2.19±0.88)％ (P=0.006),胃大体评分(4.70±2.79)比(13.90±5.28)分(P=0.009)]；Aip组显著高于Aic组[尿蔗糖排出率(2.00±0.63)％比(0.82±0.36)％(P=0.007),胃大体评分(9.90±6.60)比(4.70±2.79)分(P=0.008)].各组血浆D-乳酸、二胺氧化酶变化趋势一致:与C组比较,Ⅰ组显著升高[血浆D-乳酸(14.37±3.70)比(7.35±1.24) mg/L(P =0.036),血浆二胺氧化酶(26.37±8.09)比(16.33±5.41) U/L(P=0.006)]；Aic组显著低于1组[血浆D-乳酸(7.51±1.22)比(14.37 ±3.70) mg/L(P=0.043),血浆二胺氧化酶(19.47±5.89)比(26.37±8.09) U/L (P=0.043)],Aip组也显著低于Ⅰ组[血浆D-乳酸(7.68±1.83)比(14.37±3.70) mg/L(P=0.032),血浆二胺氧化酶(16.20±6.52)比(26.37±8.09) U/L (P=0.004)]；Aip组和Aic组比较差异无统计学意义.结论 脑梗死时下丘脑组织的CRH蛋白含量升高,胃肠道黏膜屏障破坏.中枢使用CRH受体拮抗剂α-螺旋-CRH (9-41)能缓解脑梗死相关的胃肠屏障破坏；外周使用CRH受体拮抗剂能缓解脑梗死相关的肠屏障破坏而不能缓解脑梗死相关的胃屏障破坏.脑梗死相关的胃肠屏障破坏与皮质醇及儿茶酚胺存在因果关系的可能性极小.
目的 探討促腎上腺激素釋放激素(CRH)在腦梗死胃腸屏障破壞中的作用.方法 雄性Wistar大鼠40隻,按隨機數字錶法分為假手術組(C組)、腦梗死組(Ⅰ組)、腦梗死+腦室α-螺鏇-CRH (9-41)組(Aic組)、腦梗死+腹腔α-螺鏇-CRH (9-41)組(Aip組),每組10隻.造模成功後留24 h尿檢測尿腎上腺素、去甲腎上腺素、皮質醇含量及蔗糖排齣率,造模後24 h檢測血漿二胺氧化酶(DAO)活性和D-乳痠濃度；進行胃大體Guth評分,Western-blot法檢測下丘腦組織的CRH蛋白錶達.結果 各組24h尿腎上腺素、去甲腎上腺素、24 h皮質醇含量和下丘腦組織的CRH蛋白錶達變化趨勢一緻:與C組比較,Ⅰ組顯著升高[24h尿腎上腺素(42.28±19.86)比(13.11±7.56) ng (P=0.039),去甲腎上腺素(265.96±82.09)比(156.65±60.28) ng (P =0.042),24 h皮質醇含量(239.85±73.85)比(106.13±47.47) ng (P =0.006),下丘腦組織的CRH蛋白錶達1.36±0.42比0.59±0.27 (P=0.002)],Aip組亦顯著升高[24h尿腎上腺素(77.89±34.17)比(13.11±7.56) ng (P=0.009),去甲腎上腺素(380.49±97.00)比(156.65±60.28) ng (P=0.007),24 h皮質醇含量(276.13±99.24)比(106.13±47.47) ng (P =0.007),下丘腦組織CRH蛋白錶達1.18 ±0.26比0.59±0.27 (P =0.003)],Aic組差異無統計學意義；Ⅰ組顯著高于Aic組[24 h尿腎上腺素(42.28±19.86)比(17.93±6.25) ng (P =0.036),去甲腎上腺素(265.96±82.09)比(160.50±34.88) ng (P=0.038),24h皮質醇含量(239.85±73.85)比(127.90±47.17) ng(P =0.005),下丘腦組織CRH蛋白錶達1.36±0.42比0.82±0.20 (P =0.027)],Aip組也顯著高于Aic組[24h尿腎上腺素(77.89±34.17)比(17.93±6.25) ng (P=0.008),去甲腎上腺素(380.49 ±97.00)比(160.50±34.88) ng (P=0.007),24 h皮質醇含量(276.13±99.24)比(127.90±47.17) ng (P=0.004),CRH蛋白錶達1.18±0.26比0.82±0.20 (P =0.039)].各組尿蔗糖排齣率、胃大體評分變化趨勢一緻:與C組比較,Ⅰ組顯著升高[尿蔗糖排齣率(2.19±0.88)％比(0.54±0.29)％(P=0.005),胃大體評分(13.90±5.28)比(1.50±1.43)分(P=0.003)]；Aip組亦顯著升高[尿蔗糖排齣率(2.00±0.63)％比(0.54±0.29)％ (P =0.007),胃大體評分(9.90±6.60)比(1.50±1.43)分(P =0.005)]；Aic組顯著低于Ⅰ組[尿蔗糖排齣率(0.82±0.36)％比(2.19±0.88)％ (P=0.006),胃大體評分(4.70±2.79)比(13.90±5.28)分(P=0.009)]；Aip組顯著高于Aic組[尿蔗糖排齣率(2.00±0.63)％比(0.82±0.36)％(P=0.007),胃大體評分(9.90±6.60)比(4.70±2.79)分(P=0.008)].各組血漿D-乳痠、二胺氧化酶變化趨勢一緻:與C組比較,Ⅰ組顯著升高[血漿D-乳痠(14.37±3.70)比(7.35±1.24) mg/L(P =0.036),血漿二胺氧化酶(26.37±8.09)比(16.33±5.41) U/L(P=0.006)]；Aic組顯著低于1組[血漿D-乳痠(7.51±1.22)比(14.37 ±3.70) mg/L(P=0.043),血漿二胺氧化酶(19.47±5.89)比(26.37±8.09) U/L (P=0.043)],Aip組也顯著低于Ⅰ組[血漿D-乳痠(7.68±1.83)比(14.37±3.70) mg/L(P=0.032),血漿二胺氧化酶(16.20±6.52)比(26.37±8.09) U/L (P=0.004)]；Aip組和Aic組比較差異無統計學意義.結論 腦梗死時下丘腦組織的CRH蛋白含量升高,胃腸道黏膜屏障破壞.中樞使用CRH受體拮抗劑α-螺鏇-CRH (9-41)能緩解腦梗死相關的胃腸屏障破壞；外週使用CRH受體拮抗劑能緩解腦梗死相關的腸屏障破壞而不能緩解腦梗死相關的胃屏障破壞.腦梗死相關的胃腸屏障破壞與皮質醇及兒茶酚胺存在因果關繫的可能性極小.
목적 탐토촉신상선격소석방격소(CRH)재뇌경사위장병장파배중적작용.방법 웅성Wistar대서40지,안수궤수자표법분위가수술조(C조)、뇌경사조(Ⅰ조)、뇌경사+뇌실α-라선-CRH (9-41)조(Aic조)、뇌경사+복강α-라선-CRH (9-41)조(Aip조),매조10지.조모성공후류24 h뇨검측뇨신상선소、거갑신상선소、피질순함량급자당배출솔,조모후24 h검측혈장이알양화매(DAO)활성화D-유산농도；진행위대체Guth평분,Western-blot법검측하구뇌조직적CRH단백표체.결과 각조24h뇨신상선소、거갑신상선소、24 h피질순함량화하구뇌조직적CRH단백표체변화추세일치:여C조비교,Ⅰ조현저승고[24h뇨신상선소(42.28±19.86)비(13.11±7.56) ng (P=0.039),거갑신상선소(265.96±82.09)비(156.65±60.28) ng (P =0.042),24 h피질순함량(239.85±73.85)비(106.13±47.47) ng (P =0.006),하구뇌조직적CRH단백표체1.36±0.42비0.59±0.27 (P=0.002)],Aip조역현저승고[24h뇨신상선소(77.89±34.17)비(13.11±7.56) ng (P=0.009),거갑신상선소(380.49±97.00)비(156.65±60.28) ng (P=0.007),24 h피질순함량(276.13±99.24)비(106.13±47.47) ng (P =0.007),하구뇌조직CRH단백표체1.18 ±0.26비0.59±0.27 (P =0.003)],Aic조차이무통계학의의；Ⅰ조현저고우Aic조[24 h뇨신상선소(42.28±19.86)비(17.93±6.25) ng (P =0.036),거갑신상선소(265.96±82.09)비(160.50±34.88) ng (P=0.038),24h피질순함량(239.85±73.85)비(127.90±47.17) ng(P =0.005),하구뇌조직CRH단백표체1.36±0.42비0.82±0.20 (P =0.027)],Aip조야현저고우Aic조[24h뇨신상선소(77.89±34.17)비(17.93±6.25) ng (P=0.008),거갑신상선소(380.49 ±97.00)비(160.50±34.88) ng (P=0.007),24 h피질순함량(276.13±99.24)비(127.90±47.17) ng (P=0.004),CRH단백표체1.18±0.26비0.82±0.20 (P =0.039)].각조뇨자당배출솔、위대체평분변화추세일치:여C조비교,Ⅰ조현저승고[뇨자당배출솔(2.19±0.88)％비(0.54±0.29)％(P=0.005),위대체평분(13.90±5.28)비(1.50±1.43)분(P=0.003)]；Aip조역현저승고[뇨자당배출솔(2.00±0.63)％비(0.54±0.29)％ (P =0.007),위대체평분(9.90±6.60)비(1.50±1.43)분(P =0.005)]；Aic조현저저우Ⅰ조[뇨자당배출솔(0.82±0.36)％비(2.19±0.88)％ (P=0.006),위대체평분(4.70±2.79)비(13.90±5.28)분(P=0.009)]；Aip조현저고우Aic조[뇨자당배출솔(2.00±0.63)％비(0.82±0.36)％(P=0.007),위대체평분(9.90±6.60)비(4.70±2.79)분(P=0.008)].각조혈장D-유산、이알양화매변화추세일치:여C조비교,Ⅰ조현저승고[혈장D-유산(14.37±3.70)비(7.35±1.24) mg/L(P =0.036),혈장이알양화매(26.37±8.09)비(16.33±5.41) U/L(P=0.006)]；Aic조현저저우1조[혈장D-유산(7.51±1.22)비(14.37 ±3.70) mg/L(P=0.043),혈장이알양화매(19.47±5.89)비(26.37±8.09) U/L (P=0.043)],Aip조야현저저우Ⅰ조[혈장D-유산(7.68±1.83)비(14.37±3.70) mg/L(P=0.032),혈장이알양화매(16.20±6.52)비(26.37±8.09) U/L (P=0.004)]；Aip조화Aic조비교차이무통계학의의.결론 뇌경사시하구뇌조직적CRH단백함량승고,위장도점막병장파배.중추사용CRH수체길항제α-라선-CRH (9-41)능완해뇌경사상관적위장병장파배；외주사용CRH수체길항제능완해뇌경사상관적장병장파배이불능완해뇌경사상관적위병장파배.뇌경사상관적위장병장파배여피질순급인다분알존재인과관계적가능성겁소.
Objective To investigate the central and peripheral roles of corticotrophin-releasing hormone (CRH) in cerebral infarction-related gastrointestinal barrier dysfunction.Methods Forty male Wistar rats were randomized by random number table and divided into pseudo-operation group (group C),cerebral infarction group (group Ⅰ),cerebral infarction + intracerebroventricular CRH blocker group (group Aic),and cerebral infarction + intraperitoneal CRH blocker group (group Aip).Urine samples were collected to determine the levels of epinephrine,norepinephrine,cortisol,and sucrose.At 24 hours after establishment of the models,blood samples were taken to determine the activity of diamine oxidase (DAO) and the concentration of D-lactic acid (D-lac).The stomach was taken to determine gastric Guth score,and the hypothalamus was also taken to determine tissue CRH protein expression using Western blot.Results The change of urinary cortisol and catecholamine were nearly the same with the hypothalamus CRH protein:group Ⅰ were significant higher than group C [urinary epinephrine (42.28 ± 19.86) ng vs (13.11 ± 7.56) ng (P =0.039),urinary norepinephrine (265.96 ± 82.09) ng vs (156.65 ± 60.28) ng (P =0.042),urinary cortisol (239.85 ± 73.85) ng vs (106.13 ± 47.47) ng (P =0.006),hypothalamus CRH protein 1.36 ± 0.42 vs 0.59 ± 0.27 ng (P =0.002)] ; group Aip was also significant higher than group C [urinary epinephrine (77.89 ± 34.17) ng vs (13.11 ±7.56) ng (P =0.009),urinary norepinephrine (380.49 ±97.00) ng vs (156.65 ±60.28) ng (P =0.007),urinary cortisol (276.13 ± 99.24) ng vs (106.13 ± 47.47) ng (P =0.007),hypothalamus CRH protein 1.18 ±0.26 vs 0.59 ± 0.27 (P =0.003)].The parameters were not significantly different between group Aic and group C,whereas those in group Ⅰ were significantly higher than in group Aic [urinary epinephrine (42.28 ± 19.86) ng vs (17.93 ± 6.25) ng (P =0.036),urinary norepinepthrine (265.96 ± 82.09) ng vs (160.50 ± 34.88) ng (P =0.038),urinary cortisol (239.85 ± 73.85) ng vs (127.90 ± 47.17) ng (P =0.004),hypothalamus CRH protein 1.36 ± 0.42 vs 0.82 ± 0.20 (P =0.027)] ; the parameters in group Aip were also significantly higher than in group Aic [urinary epinephrine (77.89 ±34.17) ng vs (17.93 ± 6.25) ng (P =0.008),urinary norepinephfine (380.49 ± 97.00) ng vs (160.50 ± 34.88) ng (P =0.007),urinary cortisol (276.13 ± 99.24) ng vs (127.90 ± 47.17) ng (P =0.005),and hypothalamus CRH protein 1.18 ±0.26 vs 0.82 ±0.20 (P =0.039)].The change of urine sucrose exertion and gastric Guth score were nearly the same:parameters in group Ⅰ were significantly higher than in group C [urine sucrose exertion (2.19 ±0.88)％ vs (0.54 ±0.29)％ (P =0.005) and gastric Guth score (13.90 ±5.28) score vs (1.50 ± i.43) score (P =0.003)] ; parameters in group Aip were also significantly higher than in group C [urine sucrose exertion (2.00 ± 0.63) ％ vs (0.54 ± 0.29) ％ (P =0.007) and gastric Guth score (9.90 ± 6.60) score vs (1.50 ± 1.43) score (P =0.005)] ; parameters in group Aic were significantly lower than in group Ⅰ [urine sucrose exertion (0.82 ±0.36)％ vs (2.19 ±0.88)％ (P=0.006) and gastric Guth score (4.70 ± 2.79) score vs (13.90 ±5.28) score (P =0.009)] ; paramters in group Aip were significantly higher than in group Aic [urine sucrose exertion (2.00 ± 0.63) ％ vs (0.82 ± 0.36) ％ (P =0.007) and gastric Guth score (9.90 ± 6.60) score vs (4.70 ± 2.79) score (P =0.008)].The changes of plasma DAO activity and plasma D-lac level were nearly the same:parameters in group Ⅰ were significantly higher than in group C [D-lac level (14.37 ±3.70) mg/L vs (7.35 ± 1.24) mg/L (P =0.036) and plasma DAO activity (26.37 ±8.09) U/L vs (16.33 ± 5.41) U/L (P =0.006)] ; parameters in group Aic were significantly lower than in group Ⅰ [D-lac level (7.51 ±1.22) mg/Lvs (14.37 t3.70) mg/L (P =0.043) and plasma DAO activity (19.47 ± 5.89) U/L vs (26.37 ± 8.09) U/L (P =0.043)],and parameters in group Aip were also significantly lower than in group Ⅰ [D-lac level (7.68 ± 1.83) mg/L vs (14.37 ± 3.70) mg/L (P =0.032),plasma DAO activity (16.20 ±6.52) U/L vs (26.37 ±8.09) U/L (P =0.004)] ; also,there was no significant difference between group Aip and group Aic.Conclusions After cerebral infarction,hypothalamus CRH protein expression is elevated and the gastrointestinal barrier function is destroyed.Central use of CRH blocker can decrease cerebral infarction-related gastrointestinal barrier dysfunction.Peripheral use of CRH blocker can decrease cerebral infarction-related intestinal barrier dysfunction but can not decrease cerebral infarctions-related gastric barrier dysfunction.Cerebral infarction-related gastrointestinal barrier dysfunction is not likely to be related to cortisol and catecholamine.
