医学研究生学报
醫學研究生學報
의학연구생학보
JOURNAL OF MEDICAL POSTGRADUATE
2015年
8期
809-814
,共6页
李新灵%雷钟%杜靖%贾小艳%田炜%张健%张冰
李新靈%雷鐘%杜靖%賈小豔%田煒%張健%張冰
리신령%뢰종%두정%가소염%전위%장건%장빙
右美托咪定%肾缺血再灌注%心肌组织%炎症因子
右美託咪定%腎缺血再灌註%心肌組織%炎癥因子
우미탁미정%신결혈재관주%심기조직%염증인자
Dexmedetomidine%Renal ischemia reperfusion injury%Myocardial tissue%Inflammation
目的：肾缺血再灌注对心肌组织有损伤，而右美托咪定是一种具有抗交感、镇静和镇痛等作用的新型α2肾上腺素能受体激动剂。文中探讨不同剂量右美托咪定对大鼠肾缺血再灌注心肌组织的影响。方法成年雄性Wistar大鼠40只，采用随机数字表法，分为5组（ n＝8）：假手术组（仅游离双侧肾蒂，不结扎）、缺血再灌注组（切除右肾、结扎左肾动脉120 min再灌注3 h）、右美托咪定低、中、高剂量组（分别用右美托咪定25、50、100μg／kg＋肾缺血120 min-再灌注3 h）。5组均于恢复灌注3 h时经下腔静脉采血5 mL，检测血清肌酐（creatinine， Cr）、尿素氮（blood urea nitrogen， BUN）浓度，并取肾组织和心肌组织，光镜下观察病理学结果，酶联免疫法检测白细胞介素-10（interleukin-10， IL-10）、肿瘤坏死因子-α（tumor necrosis facto-α， TNF-α）的表达。结果假手术组肾单位结构正常；肾缺血再灌注组肾小球内大量红细胞渗出，间质炎性细胞浸润，肾小管管腔内可见大量坏死脱落细胞；右美托咪定低剂量组肾小球内红细胞渗出，间质炎性细胞浸润，肾小管管腔内可见少量坏死脱落细胞；右美托咪定中剂量组部分肾小球内可见红细胞渗出，间质炎性细胞浸润，肾小管管腔内可见少量坏死脱落细胞；右美托咪定高剂量组部分肾小球内红细胞渗出，间质炎性细胞浸润，肾小管管腔内偶见坏死脱落细胞。假手术组心肌细胞排列整齐，结构正常，染色质分布均匀，细胞质染色均匀；肾缺血再灌注组心肌细胞水肿显著、空泡样变性，可见局灶凝固性坏死，大量炎性细胞的浸润，偶见成片出血；右美托咪定低剂量组心肌细胞水肿、空泡样变性，可见局灶凝固性坏死，局灶可见大量炎性细胞的浸润；右美托咪定中剂量组心肌细胞水肿，小灶区凝固性坏死，少许炎性细胞的浸润；右美托咪定高剂量组心肌细胞水肿、少许炎性细胞的浸润。与假手术组比较，缺血再灌注组，右美托咪定低、中、高剂量组血清中Cr、BUN浓度和肾组织、心肌组织中TNF-α、IL-10浓度均升高（P＜0．05）。缺血再灌注组，右美托咪定低、中、高剂量组血清中Cr浓度[（167．11±18．81、135．46±9．80、114．29±12．50、100．15±8．81）μmol／L]、BUN浓度[（13．42±1．25、11．73±1．15、10．27±0．78、9．28±0．52）mmol／L]及大鼠肾组织TNF-α浓度[（578．45±30．59、530．76±20．59、482．23±27．12、423．14±21．16）ng／L]和心肌组织中TNF-α浓度[（565．00±37．66、517．82±36．89、469．99±32．43、407．41±23．77）ng／L]表达均逐渐下降，组间两两比较差异具有统计学意义（P＜0．05）；而大鼠肾组织IL-10浓度[（97．40±14．96、117．32±13．85、147．83±27．38、168．08±22．58） ng／L]和心肌组织IL-10浓度[（105．20±3．62、124．39±14．27、165．71±31．62、202．31±20．19）ng／L]逐渐升高，组间两两比较差异具有统计学意义（P＜0．05）。结论右美托咪定可减轻大鼠肾缺血再灌注引起的心肌组织的损伤，且呈剂量依赖性，其机制与抑制炎症因子有关。
目的：腎缺血再灌註對心肌組織有損傷，而右美託咪定是一種具有抗交感、鎮靜和鎮痛等作用的新型α2腎上腺素能受體激動劑。文中探討不同劑量右美託咪定對大鼠腎缺血再灌註心肌組織的影響。方法成年雄性Wistar大鼠40隻，採用隨機數字錶法，分為5組（ n＝8）：假手術組（僅遊離雙側腎蒂，不結扎）、缺血再灌註組（切除右腎、結扎左腎動脈120 min再灌註3 h）、右美託咪定低、中、高劑量組（分彆用右美託咪定25、50、100μg／kg＋腎缺血120 min-再灌註3 h）。5組均于恢複灌註3 h時經下腔靜脈採血5 mL，檢測血清肌酐（creatinine， Cr）、尿素氮（blood urea nitrogen， BUN）濃度，併取腎組織和心肌組織，光鏡下觀察病理學結果，酶聯免疫法檢測白細胞介素-10（interleukin-10， IL-10）、腫瘤壞死因子-α（tumor necrosis facto-α， TNF-α）的錶達。結果假手術組腎單位結構正常；腎缺血再灌註組腎小毬內大量紅細胞滲齣，間質炎性細胞浸潤，腎小管管腔內可見大量壞死脫落細胞；右美託咪定低劑量組腎小毬內紅細胞滲齣，間質炎性細胞浸潤，腎小管管腔內可見少量壞死脫落細胞；右美託咪定中劑量組部分腎小毬內可見紅細胞滲齣，間質炎性細胞浸潤，腎小管管腔內可見少量壞死脫落細胞；右美託咪定高劑量組部分腎小毬內紅細胞滲齣，間質炎性細胞浸潤，腎小管管腔內偶見壞死脫落細胞。假手術組心肌細胞排列整齊，結構正常，染色質分佈均勻，細胞質染色均勻；腎缺血再灌註組心肌細胞水腫顯著、空泡樣變性，可見跼竈凝固性壞死，大量炎性細胞的浸潤，偶見成片齣血；右美託咪定低劑量組心肌細胞水腫、空泡樣變性，可見跼竈凝固性壞死，跼竈可見大量炎性細胞的浸潤；右美託咪定中劑量組心肌細胞水腫，小竈區凝固性壞死，少許炎性細胞的浸潤；右美託咪定高劑量組心肌細胞水腫、少許炎性細胞的浸潤。與假手術組比較，缺血再灌註組，右美託咪定低、中、高劑量組血清中Cr、BUN濃度和腎組織、心肌組織中TNF-α、IL-10濃度均升高（P＜0．05）。缺血再灌註組，右美託咪定低、中、高劑量組血清中Cr濃度[（167．11±18．81、135．46±9．80、114．29±12．50、100．15±8．81）μmol／L]、BUN濃度[（13．42±1．25、11．73±1．15、10．27±0．78、9．28±0．52）mmol／L]及大鼠腎組織TNF-α濃度[（578．45±30．59、530．76±20．59、482．23±27．12、423．14±21．16）ng／L]和心肌組織中TNF-α濃度[（565．00±37．66、517．82±36．89、469．99±32．43、407．41±23．77）ng／L]錶達均逐漸下降，組間兩兩比較差異具有統計學意義（P＜0．05）；而大鼠腎組織IL-10濃度[（97．40±14．96、117．32±13．85、147．83±27．38、168．08±22．58） ng／L]和心肌組織IL-10濃度[（105．20±3．62、124．39±14．27、165．71±31．62、202．31±20．19）ng／L]逐漸升高，組間兩兩比較差異具有統計學意義（P＜0．05）。結論右美託咪定可減輕大鼠腎缺血再灌註引起的心肌組織的損傷，且呈劑量依賴性，其機製與抑製炎癥因子有關。
목적：신결혈재관주대심기조직유손상，이우미탁미정시일충구유항교감、진정화진통등작용적신형α2신상선소능수체격동제。문중탐토불동제량우미탁미정대대서신결혈재관주심기조직적영향。방법성년웅성Wistar대서40지，채용수궤수자표법，분위5조（ n＝8）：가수술조（부유리쌍측신체，불결찰）、결혈재관주조（절제우신、결찰좌신동맥120 min재관주3 h）、우미탁미정저、중、고제량조（분별용우미탁미정25、50、100μg／kg＋신결혈120 min-재관주3 h）。5조균우회복관주3 h시경하강정맥채혈5 mL，검측혈청기항（creatinine， Cr）、뇨소담（blood urea nitrogen， BUN）농도，병취신조직화심기조직，광경하관찰병이학결과，매련면역법검측백세포개소-10（interleukin-10， IL-10）、종류배사인자-α（tumor necrosis facto-α， TNF-α）적표체。결과가수술조신단위결구정상；신결혈재관주조신소구내대량홍세포삼출，간질염성세포침윤，신소관관강내가견대량배사탈락세포；우미탁미정저제량조신소구내홍세포삼출，간질염성세포침윤，신소관관강내가견소량배사탈락세포；우미탁미정중제량조부분신소구내가견홍세포삼출，간질염성세포침윤，신소관관강내가견소량배사탈락세포；우미탁미정고제량조부분신소구내홍세포삼출，간질염성세포침윤，신소관관강내우견배사탈락세포。가수술조심기세포배렬정제，결구정상，염색질분포균균，세포질염색균균；신결혈재관주조심기세포수종현저、공포양변성，가견국조응고성배사，대량염성세포적침윤，우견성편출혈；우미탁미정저제량조심기세포수종、공포양변성，가견국조응고성배사，국조가견대량염성세포적침윤；우미탁미정중제량조심기세포수종，소조구응고성배사，소허염성세포적침윤；우미탁미정고제량조심기세포수종、소허염성세포적침윤。여가수술조비교，결혈재관주조，우미탁미정저、중、고제량조혈청중Cr、BUN농도화신조직、심기조직중TNF-α、IL-10농도균승고（P＜0．05）。결혈재관주조，우미탁미정저、중、고제량조혈청중Cr농도[（167．11±18．81、135．46±9．80、114．29±12．50、100．15±8．81）μmol／L]、BUN농도[（13．42±1．25、11．73±1．15、10．27±0．78、9．28±0．52）mmol／L]급대서신조직TNF-α농도[（578．45±30．59、530．76±20．59、482．23±27．12、423．14±21．16）ng／L]화심기조직중TNF-α농도[（565．00±37．66、517．82±36．89、469．99±32．43、407．41±23．77）ng／L]표체균축점하강，조간량량비교차이구유통계학의의（P＜0．05）；이대서신조직IL-10농도[（97．40±14．96、117．32±13．85、147．83±27．38、168．08±22．58） ng／L]화심기조직IL-10농도[（105．20±3．62、124．39±14．27、165．71±31．62、202．31±20．19）ng／L]축점승고，조간량량비교차이구유통계학의의（P＜0．05）。결론우미탁미정가감경대서신결혈재관주인기적심기조직적손상，차정제량의뢰성，기궤제여억제염증인자유관。
Objective Renal ischemia-reperfusion may cause myocardial injury and dexmedetomidine ( DEX)is a new alpha-2 adrenergic agonist which has the effects of antisympathia , sedation and analgesia.The article was to observe the effects of different doses of dexmedetomidine on myocardial injury induced by renal ischemia -reperfusion(I/R) in Rats. Methods 40 male Wistar rats were randomized into 5 groups(n=8 each)using a random number table: sham operation group(isolation of bilateral renal pedicles without ligation), I/R group (3 hours′reperfusion 120 minutes after the right nephrectomy and the ligation of left renal artery ), DEX low dose group, DEX middle dose group and DEX high dose group (DEX 25, 50, 100 μg/kg were respectively injected intraperitone-ally in rats of the three groups plus 3 hours′reperfusion after 120 minutes′ischemia ) .Blood samples were collected at 3 hours′reper-fusion to determine serum creatinine(Cr) and blood urea nitrogen(BUN) concentrations.Kidney and myocardial specimens were ex-tracted for microscopic examination and IL-10,TNF-αcontent were detected by ELISA. Results In sham operation group, renal structure was normal.In I/R group, a great amount of erythrocyte infiltration and interstitial infiltrating inflammatory cells were found in glomerulus and a lot of exfoliative cells were found in renal tubules .In DEX low dose group , erythrocyte infiltration and interstitial infiltrating inflammatory cells were found in glomerulus and a few exfoliative cells were found in renal tubules .In DEX middle dose group, erythrocyte infiltration and interstitial infiltrating inflammatory cells were found in partial glomerulus and a few exfoliative cells were found in renal tubules .In DEX high dose group , erythrocyte infiltration and interstitial infiltrating inflammatory cells in partial glomerulus were found and rare exfoliative cells were found in renal tubules .In sham operation group , cardiomyocytes were arranged in perfect order and normal structure , and chromatins and cytoplasms were in uniform distribution .In I/R group, edema and spongiform were obvious in cardiomyocytes , and focal coagulative necrosis was observed along with a great amount of infiltrating inflammatory cells and rare flaky bleeding .In DEX low dose group , edema and spongiform were found in cardiomyocytes , and focal coagulative necrosis was observed along with a great amount of infiltrating inflammatory cells and rare flaky bleeding .In DEX middle dose group , edema was found in cardiomyocytes , and mini focal coagulative necrosis was observed along with a small amount of infiltrating inflammatory cells.In DEX high dose group , edema was found in cardiomyocytes along with a small amount of infiltrating inflammatory cells .Com-pared with sham operation group , Cr, BUN concentrations in serum and IL-10,TNF-αcontents in kidney tissue and myocardium signif-icantly increased in I/R group, low dose group, middle dose group and high dose group(P<0.05).Compared with I/R group, IL-10 contents kidney tissue and myocardium significantly increased in small dose group (P<0.05).Cr ([167.11 ±18.81, 135.46 ± 9.80, 114.29 ±12.50, 100.15 ±8.81]μmol/L), BUN ([13.42 ±1.25, 11.73 ±1.15, 10.27 ±0.78, 9.28 ±0.52] mmol/L) concentrations in serum and TNF-αcontents in kidney tissue ([578.45 ±30.59, 530.76 ±20.59, 482.23 ±27.12, 423.14 ± 21.16]ng/L) and myocardium ([565.00 ±37.66, 517.82 ±36.89, 469.99 ±32.43, 407.41 ±23.77] ng/L) significantly de-creased in a dose-dependent manner in low , middle and high groups (P<0.05).Microscopic examination showed that the pathological changes of both kidney tissue and myocardium were significantly attenuated in low , middle and high dose group . Conclusion Dexmedetomidine can allenuate myocardial tissue injury induced by renal ischemia -reperfusion in a dose-dependent manner in rats and its mechanism may be involved with the inhibition of inflammatory factors .
