国际心血管病杂志
國際心血管病雜誌
국제심혈관병잡지
INTERNATIONAL JOURNAL OF CARDIOVASCULAR DISEASE
2014年
6期
402-405
,共4页
杨敬宁%肖敏%王学军%柴林%罗明
楊敬寧%肖敏%王學軍%柴林%囉明
양경저%초민%왕학군%시림%라명
心脏骤停后综合征%蛋白酶激活受体-1%炎症%凋亡%细胞外调节蛋白激酶
心髒驟停後綜閤徵%蛋白酶激活受體-1%炎癥%凋亡%細胞外調節蛋白激酶
심장취정후종합정%단백매격활수체-1%염증%조망%세포외조절단백격매
Post-cardiac arrest syndrome%Protease-activated receptor-1%Inflammation%Apoptosis%Extracellular regulated protein kinases
目的：探讨蛋白酶激活受体-1（PAR-1）拮抗剂对心脏骤停后综合征（PCAS）中肾损伤的影响及机制。方法：将日本大耳白兔随机分为假手术组（n ＝5）、PCAS 组（n＝10）、PAR-1拮抗剂组（n＝10）。采用窒息性心脏骤停法制备兔 PCAS 模型。PAR-1拮抗剂组于心肺复苏后10 min 给予静脉滴注 PAR-1拮抗剂 SCH79797（25μg／kg），其余各组给予等量生理盐水静脉滴注。72 h 后取股静脉血检测血清肌酐和胱抑素 C 水平；取肾组织制备石蜡切片后行 HE 染色；采用 TUNEL 法测定肾脏细胞凋亡情况；应用Western blot 测定肾组织半胱天冬酶（casepase）-3、细胞外调节蛋白激酶（ERK）活化情况。结果：与假手术组相比，PCAS 组血清肌酐和胱抑素 C 水平明显上升，肾组织有大量炎性细胞浸润，凋亡细胞数显著增多，有催化活性的 caspase-3裂解片段（cleaved caspase-3）表达增高，磷酸化 ERK （p-ERK）表达减少（P ＜0．05）。与 PCAS 组相比， PAR-1拮抗剂组肾组织损伤减轻，血清肌酐和胱抑素 C 水平明显下降，凋亡细胞数减少， cleaved caspase-3表达降低，而 p-ERK 表达显著增高（P ＜0．05）。结论：PAR-1拮抗剂 SCH79797能抑制 PCAS 兔肾组织的炎症反应和细胞凋亡，可能与 ERK 信号通路激活有关。
目的：探討蛋白酶激活受體-1（PAR-1）拮抗劑對心髒驟停後綜閤徵（PCAS）中腎損傷的影響及機製。方法：將日本大耳白兔隨機分為假手術組（n ＝5）、PCAS 組（n＝10）、PAR-1拮抗劑組（n＝10）。採用窒息性心髒驟停法製備兔 PCAS 模型。PAR-1拮抗劑組于心肺複囌後10 min 給予靜脈滴註 PAR-1拮抗劑 SCH79797（25μg／kg），其餘各組給予等量生理鹽水靜脈滴註。72 h 後取股靜脈血檢測血清肌酐和胱抑素 C 水平；取腎組織製備石蠟切片後行 HE 染色；採用 TUNEL 法測定腎髒細胞凋亡情況；應用Western blot 測定腎組織半胱天鼕酶（casepase）-3、細胞外調節蛋白激酶（ERK）活化情況。結果：與假手術組相比，PCAS 組血清肌酐和胱抑素 C 水平明顯上升，腎組織有大量炎性細胞浸潤，凋亡細胞數顯著增多，有催化活性的 caspase-3裂解片段（cleaved caspase-3）錶達增高，燐痠化 ERK （p-ERK）錶達減少（P ＜0．05）。與 PCAS 組相比， PAR-1拮抗劑組腎組織損傷減輕，血清肌酐和胱抑素 C 水平明顯下降，凋亡細胞數減少， cleaved caspase-3錶達降低，而 p-ERK 錶達顯著增高（P ＜0．05）。結論：PAR-1拮抗劑 SCH79797能抑製 PCAS 兔腎組織的炎癥反應和細胞凋亡，可能與 ERK 信號通路激活有關。
목적：탐토단백매격활수체-1（PAR-1）길항제대심장취정후종합정（PCAS）중신손상적영향급궤제。방법：장일본대이백토수궤분위가수술조（n ＝5）、PCAS 조（n＝10）、PAR-1길항제조（n＝10）。채용질식성심장취정법제비토 PCAS 모형。PAR-1길항제조우심폐복소후10 min 급여정맥적주 PAR-1길항제 SCH79797（25μg／kg），기여각조급여등량생리염수정맥적주。72 h 후취고정맥혈검측혈청기항화광억소 C 수평；취신조직제비석사절편후행 HE 염색；채용 TUNEL 법측정신장세포조망정황；응용Western blot 측정신조직반광천동매（casepase）-3、세포외조절단백격매（ERK）활화정황。결과：여가수술조상비，PCAS 조혈청기항화광억소 C 수평명현상승，신조직유대량염성세포침윤，조망세포수현저증다，유최화활성적 caspase-3렬해편단（cleaved caspase-3）표체증고，린산화 ERK （p-ERK）표체감소（P ＜0．05）。여 PCAS 조상비， PAR-1길항제조신조직손상감경，혈청기항화광억소 C 수평명현하강，조망세포수감소， cleaved caspase-3표체강저，이 p-ERK 표체현저증고（P ＜0．05）。결론：PAR-1길항제 SCH79797능억제 PCAS 토신조직적염증반응화세포조망，가능여 ERK 신호통로격활유관。
Objective:To investigate the effects and mechanism of protease-activated receptor-1 (PAR-1)antagonists on kidney injury in rabbits with post-cardiac arrest syndrome(PCAS). Methods:Japanese white rabbits were randomly divided into three groups:sham group (n=5),PCAS group(n=10)and PAR-1 antagonist group (n = 10).PCAS models were established by using asphyxia-induced cardiac arrest.Rabbits in PAR-1 antagonist group were given SCH79797 (25 μg/kg )by intravenous infusion after 10 min of cardiopulmonary resuscitation.The other two groups were given equal amount of saline.Femoral vein blood was collected to examine serum levels of creatinine and cystatin C after 72 h. Then,rabbits were sacrificed,and histomorphology and apoptosis of kidney were analyzed by HE staining and TUNEL respectively.Western blot was performed to determine the activation of casepase-3 and extracellular regulated protein kinases (ERK). Results:Compared with sham group,serum levels of creatinine and cystatin C were significantly elevated in PCAS group,and increased apoptosis, inflammatory cells infiltration,elevated expression of cleaved caspase-3,and down-regulated ERK phosphorylation (p-ERK)were also observed in kidney of PCAS rabbits (P <0.05 ).Compared with PCAS group,the serum levels of cystatin C and creatinine were markedly reduced in PAR-1 antagonist group,the injury and apoptosis of kidney were attenuated and level of cleaved caspase-3 was decreased, but level of ERK phosphorylation was significantly increased in PAR-1 antagonist group (P <0.05). Conclusion:PAR-1 antagonist SCH79797 inhibits inflammation and apoptosis in kidney possibly by activating ERK pathway in rabbits with PCAS.
