国际生物医学工程杂志
國際生物醫學工程雜誌
국제생물의학공정잡지
International Journal of Biomedical Engineering
2015年
4期
206-210,后插4
,共6页
李锐%李丹丹%杨霞%杨冰%屈扬扬%张玲
李銳%李丹丹%楊霞%楊冰%屈颺颺%張玲
리예%리단단%양하%양빙%굴양양%장령
心肌肥厚%G蛋白偶联受体激酶%氧化应激%N-乙酰半胱氨酸
心肌肥厚%G蛋白偶聯受體激酶%氧化應激%N-乙酰半胱氨痠
심기비후%G단백우련수체격매%양화응격%N-을선반광안산
Cardiac hypertrophy%G protein-coupled receptor kinases%Oxidative stress%N-acetylcysteine
目的 探讨持久兴奋β受体诱导病理性心肌肥厚机制中,氧化应激水平升高与GRK5之间的关系.方法 雄性SD大鼠(180～200g),按照随机原则分为对照组(CTRL)、N-乙酰半胱氨酸(NAC)组(CTRL+NAC)、异丙肾上腺素(ISO)组(ISO)及ISO注射辅以NAC组(ISO+NAC),6只/组.ISO组通过腹腔注射给予IS0 3 mg/(kg·d),对照组给予腹腔注射等量生理盐水,NAC组通过饮用水给药15g/L,共2周,分别检测各组大鼠血压、心脏质量指数(HMI)、心肌组织学变化、心肌NOX4及GRK5的表达变化.结果 与CTRL组比较,ISO组大鼠HMI明显升高[(3.99±0.10) mg/gvs(3.31±0.13) mg/g],其差异有统计学意义(P＜0.05),心肌横截面积明显增大[(11 117.00±387.57) μm2 vs(4 572.23± 176.39)μm2],其差异有统计学意义(P＜0.05);ISO+NAC组大鼠的HMI[(3.56±0.12) mg/g]、心肌细胞横截面积[(6 160.33±141.44) μm2]均明显低于ISO组大鼠,其差异均具有统计学意义(P＜0.05);ISO组大鼠心肌NOX4蛋白表达水平明显高于CTRL组(10.59±1.61 vs 4.35±1.65),其差异具有统计学意义(P＜0.05),NAC明显降低了ISO诱导的NOX4表达增加(4.67±1.25 vs 10.59±1.61),其差异具有统计学意义(P＜0.05);用Westren blot、免疫组化技术检测心肌GRK5表达情况,结果显示ISO组与CTRL组、ISO+NAC组与ISO组差异均无统计学意义(P＞0.05);同时RT-qPCR技术检测心肌GRK5 mRNA表达水平亦发现ISO与CTRL、ISO+NAC与ISO组的差异均无统计学意义(P＞0.05);鼠尾动脉血压测量结果显示在4组实验动物间差异均无统计学意义(P＞0.05);NAC组各项指标与CTRL组大鼠无差异.结论 持久兴奋β AR诱发病理性心肌肥厚机制中,GRK5可能未参与氧化应激通路对致肥厚因子的调节,有待进一步体外实验证明.
目的 探討持久興奮β受體誘導病理性心肌肥厚機製中,氧化應激水平升高與GRK5之間的關繫.方法 雄性SD大鼠(180～200g),按照隨機原則分為對照組(CTRL)、N-乙酰半胱氨痠(NAC)組(CTRL+NAC)、異丙腎上腺素(ISO)組(ISO)及ISO註射輔以NAC組(ISO+NAC),6隻/組.ISO組通過腹腔註射給予IS0 3 mg/(kg·d),對照組給予腹腔註射等量生理鹽水,NAC組通過飲用水給藥15g/L,共2週,分彆檢測各組大鼠血壓、心髒質量指數(HMI)、心肌組織學變化、心肌NOX4及GRK5的錶達變化.結果 與CTRL組比較,ISO組大鼠HMI明顯升高[(3.99±0.10) mg/gvs(3.31±0.13) mg/g],其差異有統計學意義(P＜0.05),心肌橫截麵積明顯增大[(11 117.00±387.57) μm2 vs(4 572.23± 176.39)μm2],其差異有統計學意義(P＜0.05);ISO+NAC組大鼠的HMI[(3.56±0.12) mg/g]、心肌細胞橫截麵積[(6 160.33±141.44) μm2]均明顯低于ISO組大鼠,其差異均具有統計學意義(P＜0.05);ISO組大鼠心肌NOX4蛋白錶達水平明顯高于CTRL組(10.59±1.61 vs 4.35±1.65),其差異具有統計學意義(P＜0.05),NAC明顯降低瞭ISO誘導的NOX4錶達增加(4.67±1.25 vs 10.59±1.61),其差異具有統計學意義(P＜0.05);用Westren blot、免疫組化技術檢測心肌GRK5錶達情況,結果顯示ISO組與CTRL組、ISO+NAC組與ISO組差異均無統計學意義(P＞0.05);同時RT-qPCR技術檢測心肌GRK5 mRNA錶達水平亦髮現ISO與CTRL、ISO+NAC與ISO組的差異均無統計學意義(P＞0.05);鼠尾動脈血壓測量結果顯示在4組實驗動物間差異均無統計學意義(P＞0.05);NAC組各項指標與CTRL組大鼠無差異.結論 持久興奮β AR誘髮病理性心肌肥厚機製中,GRK5可能未參與氧化應激通路對緻肥厚因子的調節,有待進一步體外實驗證明.
목적 탐토지구흥강β수체유도병이성심기비후궤제중,양화응격수평승고여GRK5지간적관계.방법 웅성SD대서(180～200g),안조수궤원칙분위대조조(CTRL)、N-을선반광안산(NAC)조(CTRL+NAC)、이병신상선소(ISO)조(ISO)급ISO주사보이NAC조(ISO+NAC),6지/조.ISO조통과복강주사급여IS0 3 mg/(kg·d),대조조급여복강주사등량생리염수,NAC조통과음용수급약15g/L,공2주,분별검측각조대서혈압、심장질량지수(HMI)、심기조직학변화、심기NOX4급GRK5적표체변화.결과 여CTRL조비교,ISO조대서HMI명현승고[(3.99±0.10) mg/gvs(3.31±0.13) mg/g],기차이유통계학의의(P＜0.05),심기횡절면적명현증대[(11 117.00±387.57) μm2 vs(4 572.23± 176.39)μm2],기차이유통계학의의(P＜0.05);ISO+NAC조대서적HMI[(3.56±0.12) mg/g]、심기세포횡절면적[(6 160.33±141.44) μm2]균명현저우ISO조대서,기차이균구유통계학의의(P＜0.05);ISO조대서심기NOX4단백표체수평명현고우CTRL조(10.59±1.61 vs 4.35±1.65),기차이구유통계학의의(P＜0.05),NAC명현강저료ISO유도적NOX4표체증가(4.67±1.25 vs 10.59±1.61),기차이구유통계학의의(P＜0.05);용Westren blot、면역조화기술검측심기GRK5표체정황,결과현시ISO조여CTRL조、ISO+NAC조여ISO조차이균무통계학의의(P＞0.05);동시RT-qPCR기술검측심기GRK5 mRNA표체수평역발현ISO여CTRL、ISO+NAC여ISO조적차이균무통계학의의(P＞0.05);서미동맥혈압측량결과현시재4조실험동물간차이균무통계학의의(P＞0.05);NAC조각항지표여CTRL조대서무차이.결론 지구흥강β AR유발병이성심기비후궤제중,GRK5가능미삼여양화응격통로대치비후인자적조절,유대진일보체외실험증명.
Objective To explore the role of GRK5 in sustained β adrenergic receptor (βAR)-stimulated increased levels of oxidative stress.Methods Male SD rats (180-200 g) were separated into 4 groups according to the random principal: control group (CTRL), control with NAC supplement group (CTRL+NAC), ISO treated group (ISO), and ISO treated with NAC supplement group (ISO+NAC), with 6 rats in each group.ISO group was treated by method of intraperitoneal injection for 3 mg/(kg· d).CTRL rats received same volume of physiological saline by same method, while NAC was treated by supplement in drinking water for 15 g/L per day.After 2 weeks of treatment, BP, heart mass index (HMI), histology changes, expression of NOX4 and GRK5 of myocardium was examined.Results HMI of ISO rats was significantly higher than that of the CTRL group [(3.99±0.10 vs 3.31±0.13) mg/g, P＜0.05], and the cardio-myocyte cross-sectional area of ISO group was also significantly increased compared with CTRL group [(11 117.00±387.57 vs 4572.23±176.39) μm, P＜O.05].ISO+NAC significantly reduced the ISO-induced increases of heart weight index (3.56±0.12 mg/g, vs ISO, P＜0.05) and myocyte cross-sectional area (6160.33±141.44 μm2, vs ISO,P＜0.05).The immunohistochemistry results showed that the expression of myocardial NOX4 of ISO group was significantly higher than that of CTRL group [(10.59±1.61 vs 4.35±1.65), P＜0.05], and NAC reduced the ISO induced NOX4 expression increase [(4.67±1.25 vs 10.59±1.61), P＜0.05].Western Blot and immunohistochemistry were used to detect the protein expression of myocardial GRK5.Both results showed that there were no significant differences between ISO and CTRL, ISO+NAC and ISO group (P＞0.05).RT-qPCR detected no significant differences of myocardial GRK5 mRNA expression between ISO and CTRL, ISO+NAC and ISO groups (P＞0.05).Arterial blood pressure showed no significant difference among the 4 groups of rats (P＞0.05).No significant differences were found between rats from CTRL+NAC and CTRL group.Conclusions In the mechanism of sustained βAR-stimulated cardiac hypertrophy, GRK5 may not participate the regulation of hypertrophy-induced factor, and this process needs to be proved in further study.
