中国中西医结合急救杂志
中國中西醫結閤急救雜誌
중국중서의결합급구잡지
INTEGRATED TRADITIONAL CHINESE AND WESTERN MEDICINE IN PRACTICE OF CRITICAL CARE MEDICINE
2014年
4期
266-269
,共4页
吉春玲%瞿详%任亦频%周厚荣%杨秀林%张谦
吉春玲%瞿詳%任亦頻%週厚榮%楊秀林%張謙
길춘령%구상%임역빈%주후영%양수림%장겸
脓毒症%心肌组织水通道蛋白-1%细胞因子%肿瘤坏死因子-α%白细胞介素-6%心肌组织含水量%右美托咪定
膿毒癥%心肌組織水通道蛋白-1%細胞因子%腫瘤壞死因子-α%白細胞介素-6%心肌組織含水量%右美託咪定
농독증%심기조직수통도단백-1%세포인자%종류배사인자-α%백세포개소-6%심기조직함수량%우미탁미정
Sepsis%Myocardial tissue aquaporin-1%Cytokine%Tumor necrosis factor-α%Interleukin-6%Myocardial water content%Dexmedetomidine
目的：研究脓毒症大鼠心肌组织水通道蛋白-1（AQP-1）水平的变化规律，并比较AQP-1与心肌细胞炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）及心肌组织含水量的相关性，探讨右美托咪定对脓毒症大鼠心肌的保护作用及可能机制。方法将90只雄性SD 大鼠按随机数字表法分为假手术组、脓毒症模型组和右美托咪定组，每组30只。采用盲肠结扎穿孔术（CLP）复制大鼠脓毒症模型；假手术组仅开腹、关腹，不行CLP。右美托咪定组于术前0.5 h静脉注射右美托咪定1μg/kg，浓度为2μg/mL，模型组和假手术组大鼠术后皮下注射生理盐水5 mL/kg。于术后2、12、24、48、72 h处死6只大鼠取出心脏，采用酶联免疫吸附试验（ELISA）测定各时间点心肌组织匀浆中AQP-1含量及炎症细胞因子TNF-α、IL-6水平，利用干湿重法检测心肌组织含水量，并比较AQP-1与TNF-α、IL-6及心肌组织含水量的相关性。结果模型组术后2 h起心肌组织AQP-1、TNF-α及IL-6水平均较假手术组明显升高；随时间延长，AQP-1水平及心肌组织含水量有所降低，但TNF-α及IL-6水平却持续增高。右美托咪定组除术后72 h心肌组织含水量外，从术后2 h起上述各指标即均较模型组明显降低〔AQP-1（ng/g）：9.29±0.15比9.73±0.26，TNF-α（pg/g）：109.47±8.41比128.13±7.36，IL-6（pg/g）：232.95±20.56比279.71±22.24，心肌组织含水量：（74.82±6.37）%比（75.62±6.39）%，均P＜0.05〕，但仍高于假手术组。相关性分析显示，脓毒症大鼠AQP-1与早期心肌组织含水量（r＝0.418，P＝0.001）和晚期心肌组织含水量（r＝0.235，P＝0.022）的变化呈正相关，与早期（术后2 h）细胞因子TNF-α（r＝0.235，P＝0.021）及IL-6（r＝0.345，P＝0.003）浓度变化呈正相关，与晚期（术后72 h）细胞因子TNF-α（r＝-0.408，P＝0.037）及IL-6（r＝-0.276，P＝0.002）浓度变化呈负相关。结论脓毒症大鼠早期即出现明显心肌损伤，导致AQP-1的过度表达，从而引起心肌细胞水肿；右美托咪定可通过减少心肌组织AQP-1的表达及心肌炎症细胞因子水平进而减轻心肌细胞水肿，而发挥心肌保护作用。
目的：研究膿毒癥大鼠心肌組織水通道蛋白-1（AQP-1）水平的變化規律，併比較AQP-1與心肌細胞炎癥因子腫瘤壞死因子-α（TNF-α）、白細胞介素-6（IL-6）及心肌組織含水量的相關性，探討右美託咪定對膿毒癥大鼠心肌的保護作用及可能機製。方法將90隻雄性SD 大鼠按隨機數字錶法分為假手術組、膿毒癥模型組和右美託咪定組，每組30隻。採用盲腸結扎穿孔術（CLP）複製大鼠膿毒癥模型；假手術組僅開腹、關腹，不行CLP。右美託咪定組于術前0.5 h靜脈註射右美託咪定1μg/kg，濃度為2μg/mL，模型組和假手術組大鼠術後皮下註射生理鹽水5 mL/kg。于術後2、12、24、48、72 h處死6隻大鼠取齣心髒，採用酶聯免疫吸附試驗（ELISA）測定各時間點心肌組織勻漿中AQP-1含量及炎癥細胞因子TNF-α、IL-6水平，利用榦濕重法檢測心肌組織含水量，併比較AQP-1與TNF-α、IL-6及心肌組織含水量的相關性。結果模型組術後2 h起心肌組織AQP-1、TNF-α及IL-6水平均較假手術組明顯升高；隨時間延長，AQP-1水平及心肌組織含水量有所降低，但TNF-α及IL-6水平卻持續增高。右美託咪定組除術後72 h心肌組織含水量外，從術後2 h起上述各指標即均較模型組明顯降低〔AQP-1（ng/g）：9.29±0.15比9.73±0.26，TNF-α（pg/g）：109.47±8.41比128.13±7.36，IL-6（pg/g）：232.95±20.56比279.71±22.24，心肌組織含水量：（74.82±6.37）%比（75.62±6.39）%，均P＜0.05〕，但仍高于假手術組。相關性分析顯示，膿毒癥大鼠AQP-1與早期心肌組織含水量（r＝0.418，P＝0.001）和晚期心肌組織含水量（r＝0.235，P＝0.022）的變化呈正相關，與早期（術後2 h）細胞因子TNF-α（r＝0.235，P＝0.021）及IL-6（r＝0.345，P＝0.003）濃度變化呈正相關，與晚期（術後72 h）細胞因子TNF-α（r＝-0.408，P＝0.037）及IL-6（r＝-0.276，P＝0.002）濃度變化呈負相關。結論膿毒癥大鼠早期即齣現明顯心肌損傷，導緻AQP-1的過度錶達，從而引起心肌細胞水腫；右美託咪定可通過減少心肌組織AQP-1的錶達及心肌炎癥細胞因子水平進而減輕心肌細胞水腫，而髮揮心肌保護作用。
목적：연구농독증대서심기조직수통도단백-1（AQP-1）수평적변화규률，병비교AQP-1여심기세포염증인자종류배사인자-α（TNF-α）、백세포개소-6（IL-6）급심기조직함수량적상관성，탐토우미탁미정대농독증대서심기적보호작용급가능궤제。방법장90지웅성SD 대서안수궤수자표법분위가수술조、농독증모형조화우미탁미정조，매조30지。채용맹장결찰천공술（CLP）복제대서농독증모형；가수술조부개복、관복，불행CLP。우미탁미정조우술전0.5 h정맥주사우미탁미정1μg/kg，농도위2μg/mL，모형조화가수술조대서술후피하주사생리염수5 mL/kg。우술후2、12、24、48、72 h처사6지대서취출심장，채용매련면역흡부시험（ELISA）측정각시간점심기조직균장중AQP-1함량급염증세포인자TNF-α、IL-6수평，이용간습중법검측심기조직함수량，병비교AQP-1여TNF-α、IL-6급심기조직함수량적상관성。결과모형조술후2 h기심기조직AQP-1、TNF-α급IL-6수평균교가수술조명현승고；수시간연장，AQP-1수평급심기조직함수량유소강저，단TNF-α급IL-6수평각지속증고。우미탁미정조제술후72 h심기조직함수량외，종술후2 h기상술각지표즉균교모형조명현강저〔AQP-1（ng/g）：9.29±0.15비9.73±0.26，TNF-α（pg/g）：109.47±8.41비128.13±7.36，IL-6（pg/g）：232.95±20.56비279.71±22.24，심기조직함수량：（74.82±6.37）%비（75.62±6.39）%，균P＜0.05〕，단잉고우가수술조。상관성분석현시，농독증대서AQP-1여조기심기조직함수량（r＝0.418，P＝0.001）화만기심기조직함수량（r＝0.235，P＝0.022）적변화정정상관，여조기（술후2 h）세포인자TNF-α（r＝0.235，P＝0.021）급IL-6（r＝0.345，P＝0.003）농도변화정정상관，여만기（술후72 h）세포인자TNF-α（r＝-0.408，P＝0.037）급IL-6（r＝-0.276，P＝0.002）농도변화정부상관。결론농독증대서조기즉출현명현심기손상，도치AQP-1적과도표체，종이인기심기세포수종；우미탁미정가통과감소심기조직AQP-1적표체급심기염증세포인자수평진이감경심기세포수종，이발휘심기보호작용。
Objective To study the regulation of aquaporin-1(AQP-1)changes in the heart of septic rats, compare the correlations of the AQP-1 with myocardial cytokines tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6),and myocardial tissue water content,and to investigate the dexmedetomidine protective effect on myocardia in septic rats and its possible mechanism. Methods According to the random number table methods,90 male Sprague-Dawley(SD)rats were divided into sham operation group,sepsis model group and dexmedetomidine group, 30 rats in each group. The rat sepsis model was established by cecal ligation and puncture(CLP). In the sham operation group,the animal abdomen was only opened and closed without CLP. Half hour before operation in dexmedetomidine group,dexmedetomidine 1μg/kg(2μg/mL)was injected into the vein,while in the model and sham groups,saline 5 mL/kg was subcutaneously injected into the rat after the operation. At 2,12,24,48,72 hours after operation,6 rats were sacrificed and their hearts removed at one time point in a group. Enzyme linked immunosorbent assay(ELISA)was used to detect the content of AQP-1 and the levels of the TNF-α,IL-6 in the myocardial tissue homogenate at all time points,the myocardial tissue water content was detected by dry wet weight,and the correlations between AQP-1 and TNF-α,IL-6 and between AQP-1 and myocardial tissue water content were compared. Results From 2 hours after operation,the levels of the AQP-1,TNF-αand IL-6 in model group were significantly higher than those in the sham operation group;with prolongation of time,the level of AQP-1 and myocardial tissue water content were decreased, but the levels of TNF-α and IL-6 were persistently increased. From 2 hours after operation in dexmedetomidine group,all the above indexes except myocardial tissue water content at 72 hours after operation were significantly lower than those in the model group〔AQP-1(ng/g):9.29±0.15 vs. 9.73±0.26,TNF-α(pg/g):109.47±8.41 vs. 128.13±7.36,IL-6(pg/g):232.95±20.56 vs. 279.71±22.24,myocardial tissue water content:(74.82±6.37)%vs.(75.62±6.39)%,all P<0.05〕,but still higher than those of the sham operation group. The correlation analyses for the septic group showed that the change of AQP-1 was positively correlated to the myocardial water content in early stage(r=0.418,P=0.001)and later stage(r=0.235,P=0.022),and the changes of the AQP-1 in early stage (at post-operative 2 hours)were positively correlated to the concentration changes of the cytokines TNF-α(r=0.235,P=0.021)and IL-6(r=0.345,P=0.003),but in the later stage(at post-operative 72 hours)were negatively correlated with the changes of TNF-α(r=-0.408,P=0.037)and IL-6(r=-0.276,P=0.002). Conclusions In the early stage of septic rats,there is obvious myocardial injury,resulting in the over expression of AQP-1 and the occurrence of myocardial edema,dexmedetomidine can play a role in myocardial protection in such rats and its mechanism is possibly related to the reduction of the expression of AQP-1 and the levels of inflammatory cytokines, and in turn the alleviation of myocardial cell edema.
