缺血后处理对保护皮瓣的作用机制研究

目的：缺血后处理已经在心、肾等器官上广泛应用,进行相关研究进一步探究缺血后处理对皮瓣有否保护作用。方法：健康成年新西兰大白兔,分为3组。A组为给予缺血后处理;B组为再灌注前5min给予A2A阻滞剂SCH58261＋缺血后处理。C组,直接应用微血管夹阻断腹壁浅血管持续缺血6h后,恢复正常血供。分别进行中性粒细胞浸润,MPO含量和皮瓣存活率检测。结果：新西兰大白兔完全存活。B、C组相比较,中性粒细胞计数以及MPO含量也未见统计学差别（P〉0.005）。实验组皮瓣存活面积比较,B与C相比较,无统计学意义（P〉0.005）,但是A与B、C相比较,上述指标两两之间都有统计学意义差别（P〈0.005）。结论：缺血后处理对皮瓣再灌注损伤有保护作用,该作用可能和A2A受体性质有关。     

腺苷A2A受体激活缺血后处理保护皮瓣作用研究

目的：缺血后处理需要反复夹闭血管蒂,可能对血管造成机械性损伤。药物缺血后处理成为缺血后处理的发展方向。腺苷A2A是调控皮瓣炎症的关键靶点,进行相关研究进一步探究腺苷A2A激活缺血后处理对皮瓣有否保护作用。方法：健康成年新西兰大白兔,分为3组。A组为假手术组;B组为缺血再灌注损伤组;C组,再灌注前5min注射腺苷A2A激活剂。分别进行皮瓣存活率检测和ELISA检测TNF以及IL-6。结果：腺苷A2A激活剂组皮瓣存活率高,炎症因子检测活性低于缺血再灌注损伤组。结论：腺苷A2A激活剂缺血后处理可以抑制炎症因子,具有保护皮瓣作用。运用腺苷A2A受体激活缺血后处理可能成为保护皮瓣的新措施。     

阿霉素预处理替代缺血预处理提供鼠皮瓣缺血耐受的实验研究

目的探讨阿霉素预处理提供鼠皮瓣缺血耐受的可能性及其作用机制。方法健康成年SD大鼠24只,雌雄各半,体重250～300 g,随机分为A、B、C 3组(n=8)。于各组大鼠腹部制备以腹壁浅血管-神经束为蒂、大小为6 cm×3 cm的岛状皮瓣,A组不作处理;B组用微血管夹阻断腹壁浅血管血流10 min,松开后再灌注10 min,反复4次;C组经腹壁浅静脉推注阿霉素(1 mg/kg)。24 h后于皮瓣蒂部夹闭腹壁浅血管4 h,再灌注2 h,制备缺血再灌注损伤模型。术后观察大鼠存活情况,于缺血再灌注损伤后0、8、12、24、30 h各组取皮瓣检测丙二醛(malonyldiadehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)含量;于缺血再灌注损伤后7 d测量皮瓣成活率后处死大鼠,取皮瓣行组织学观察。结果实验中共5只大鼠死亡,其中A、B组各1只,C组3只,均给予补充。缺血再灌注损伤后7 d,A组皮瓣成活率为10.10%±0.43%,小于B组91.63%±1.76%及C组92.75%±1.48%,差异均有统计学意义(P<0.05);B组与C组比较,差异无统计学意义(t=0.29,P=0.77)。缺血再灌注损伤后0 h 3组间MDA和SOD含量比较,差异均无统计学意义(P>0.05);8 h后各时间点A组与B、C组比较,差异均有统计学意义(P<0.05),B组与C组比较差异无统计学意义(P>0.05)。组织学观察示,A组炎性细胞浸润较B、C组明显,纤维增生减弱;B组与C组皮瓣组织学改变相似。结论阿霉素预处理可以提供鼠皮瓣缺血耐受,保护皮瓣减轻缺血再灌注损伤,其机制可能与诱导内源性保护物质的产生有关。     

缓释bFGF促进缺血再灌注损伤皮瓣成活的实验研究

目的 研究缓释bFGF对缺血再灌注损伤皮瓣的效应.方法 采用酸性明胶水凝胶微球AGHMs为bFGF的载体,于10周龄20只雄性健康的Fisher大鼠背部制备对称性缺血再灌注损伤岛状皮瓣,即每只鼠2例皮瓣,共制备40例皮瓣;以CAM快速热成像仪检测皮瓣的缺血及再灌注;再灌注前注射AGHMs+bFGF的溶液,分组为:对照A组(n=10例)为AGHM+PBS溶液;实验组为bFGF+AGHMs+PBS溶液,其中的bFGF分别为20μg(设为B组,n=10例)、50μg(设为C组,n=10例)和150μg(设为D组,n=10例).手术后第7天对皮瓣成活率、微小血管成像、组织学及免疫组化检查进行评估.结果 A、B、C、D组皮瓣的成活率分别为(52.27±10,20)%、(64.00±8.20)%、(64.30±10.10)%及(78.47±11.90)%.D组皮瓣成活率与其他3组相比,其差异有统计学意义(P<0.01).微小血管成像及组织学检查显示,D组的微小血管多于其他组;电镜检查显示,A、B、C组的组织损伤较重,D组的损伤轻微.免疫组化(VEGF,TGF-β1,TGF-β2,TGF-β3,bFGF)结果相近,即D组的阳性染色表面积与其他组相比,其差异有统计学意义(P<0.01);但A、B、C组之间相比,其筹异无统计学意义(P>0.1).结论 持续释放的bFGF可以上调局部组织VEGF及TGF的释放,促进新生血管的形成,从而提高缺血再灌注损伤皮瓣的成活率.     

缺血后处理对兔小肠缺血再灌注损伤的影响

目的评价缺血后处理对兔小肠缺血再灌注损伤的影响。方法30只新西兰大白兔随机分为3组（n=10）,缺血再灌注组（I/R组）夹闭肠系膜上动脉（SMA）1h,再灌注3h,制备肠缺血再灌注模型;缺血预处理组（IPr组）夹闭SMA 5min,再灌注5min,重复3次后夹闭SMA 1h,再灌注3h;缺血后处理组（IPo组）夹闭SMA 1h,再灌注10s,缺血10s,重复3次后再灌注3h。再灌注3h后在回盲末端10cm处取0.5cm小肠段,电镜下观察肠上皮细胞线粒体结构,测定线粒体二维形态计量学参数和三维形态计量学参数;另取60cm相邻小肠段,测定肠上皮细胞线粒体呼吸控制率（RCR）和线粒体内细胞色素C含量。结果与I/R组比较,IPr组和IPo组线粒体的数目、周长、面积密度、粒子数密度及比表面增大,线粒体的面积、最大直径、最小直径及等效直径减小,线粒体RCR及细胞色素C含量升高,IPr组线粒体体积密度增加（P〈0.05）,3组间形状因子比较差异无统计学意义（P〉0.05）。电镜下IPr组和IPo组线粒体结构损伤较I/R组减轻。结论缺血后处理可减轻兔小肠缺血再灌注损伤。     

芬太尼后处理、肢体远隔缺血后处理和缺血后处理对大鼠心肌缺血/再灌注初期室性心律失常的影响

目的 对比观察芬太尼后处理、远隔缺血后处理和缺血后处理3种干预措施抑制大鼠心肌缺血/再灌注初期室性心律失常作用的差别.方法 将73只成年雄性SD大鼠(体重250 g～350 g)麻醉后按随机数字表法随机分为9组:空白对照组(S组,n=5);对照组(C组,n=7);芬太尼后处理组(F组,n=9);肢体远隔缺血后处理组(R组,n=9);缺血后处理组(P组,n=8);联合应用芬太尼后处理和肢体远隔缺血后处理组(F-R组,n=9);联合应用芬太尼后处理和缺血后处理组(F-P组,n=8);联合应用肢体远隔缺血后处理和缺血后处理组(R-P组,n=9);联合应用芬太尼后处理、肢体远隔缺血后处理和缺血后处理组(F-R-P组,n=9).所有大鼠开胸后采用丝线套扎其冠状动脉左前降支(left anterior descending coronary artery,LAD)做成活结.除S组之外,所有大鼠接受局部心肌缺血30 min和再灌注60 min的处理.C组不采用任何干预措施;F组、F-R组、F-P组和F-R-P组在LAD结扎15 min时缓慢静脉注射芬太尼30 μg/kg;R组、F-R组、R-P组和F-R-P组在LAD结扎15 min时结扎大鼠双下肢造成肢体缺血10 min后恢复双下肢血流灌注;P组、F-P组、R-P组和F-R-P组开放实施再灌注的初期连续实施3个循环的开放LAD 20 s/阻断LAD 20 s的缺血后处理.记录缺血期和再灌期前30 min内的心律失常评分(AS评分)以及室性心动过速(ventricular tachycardia,VT)和心室纤颤(ventricular fibrillation,VF)的发生率和持续时间.结果 缺血期VT和VF的发生率、VT或VF的持续时间以及AS评分在C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组无统计学差异.C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期AS评分的中位数分别为4、2、2、1、2、1、1和2.与C组比较,其余各组再灌注初期室性心律失常发生显著减少;再灌注初期的VT持续时间和AS在F组和R组之间无统计学差异,但F-R组再灌注初期的VT持续时间则显著降低.与F组和R组比较,P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期的VT持续时间和室性心律失常评分显著减低. 结论 与芬太尼后处理和远隔缺血后处理比较,缺血后处理可更有效抑制再灌注初期室性心律失常的发生.联合应用芬太尼后处理和远隔缺血后处理后,抑制心肌再灌注初期室性心律失常的作用相对增强.     

七氟醚预处理对大鼠脊髓缺血再灌注损伤的影响及自噬在其中的作用

目的 评价七氟醚预处理对大鼠脊髓缺血再灌注损伤的影响及自噬在其中的作用.方法 成年雄性SD大鼠45只,体重420～450 g,采用随机数字表法分为5组(n=9):对照组(Con组)、脊髓缺血再灌注组(I/R组)、七氟醚预处理组(Sevo组)、特异性自噬抑制剂3-甲基腺嘌呤组(3-MA组)和3-MA+七氟醚预处理组(3-MA+ Sevo组).I/R组胸主动脉球囊阻断+体循环低血压制备大鼠脊髓缺血再灌注模型,Sevo组于缺血前24h时吸入3.4％七氟醚2h,3-MA组和3-MA+ Sevo组分别于再灌注即刻和吸入七氟醚前15 min时鞘内注射20出3-MA(10 mmol/L).于再灌注24h时采用神经功能缺陷评分(NDS评分)法评价大鼠神经功能,随后处死取脊髓,Western blot法检测LC3B、Beclin 1、Bcl-2蛋白的表达水平.结果 与Con组比较,I/R组脊髓LC3B、Beclin 1蛋白表达上调,Bcl-2蛋白表达下调,NDS评分升高(P＜0.05);与I/R组比较,Sevo组、3-MA组和3-MA+ Sevo组脊髓LC3B、Beclin 1蛋白表达下调,Bcl-2蛋白表达上调,NDS评分降低(P＜0.05);Sevo组、3-MA组和3-MA+ Sevo组各指标比较差异无统计学意义(P＞0.05).结论 七氟醚预处理可减轻大鼠脊髓缺血再灌注损伤,其机制可能与上调Bcl-2,抑制自噬溶酶体途径,减轻自噬有关.     

异氟醚后处理对兔心肌缺血-再灌注损伤的影响

目的 观察异氟醚后处理对兔心肌缺血-再灌注损伤的影响及可能的信号机制.方法 60只雄性新西兰白兔,体重2.5～3.0 kg,模型制备成功后随机均分为五组:假手术组(A组);缺血-再灌注组(B组);缺血后处理组(C组);异氟醚后处理组(D组);异氟醚后处理+ PI3K抑制剂(Wortmannin)组(E组).于缺血前即刻(T0)、缺血30 min(T1)、再灌注30 min(T2)、60 min(T3)及120 min(T4)记录HR、MAP;灌注结束TTC法染色心肌切片计算心肌梗死面积百分比,TUNEL法检测心肌细胞凋亡计算凋亡指数(AI);蛋白印迹检测磷酸化Akt(p-Akt)及总Akt(t-Akt)表达水平.结果 T2～T时五组HR明显慢于、MAP明显低于T0时(P＜0.05).与B组比较,C、D组心肌梗死面积缩小,AI降低(P＜0.05),p-Akt表达升高(P＜0.05).E组p-Akt表达明显低于C、D组(P＜0.05).结论 异氟醚后处理通过PI3K/Akt信号通路减轻兔心肌缺血-再灌注损伤.     

右美托咪定预处理通过激活PINK1/Parkin通路介导的线粒体自噬减轻小鼠肝缺血再灌注后急性肾损伤

目的:探究右美托咪定预处理对肝缺血再灌注小鼠肾脏线粒体自噬和肾功能的影响.方法:C57BL/6两周龄的小鼠采用夹闭肝左叶、中叶脉管(门脉、动脉与胆道)的共干的方法制备70％肝缺再灌注损伤模型.随机分为4组(n=10):假手术组(S组)、肝缺血再灌注组(IR组)、右美托咪定组(D组)与自噬抑制剂3-甲基腺嘌呤(3-MA)...     

自噬标记性分子LC3-Ⅱ在肝脏缺血再灌注损伤中的研究

肝癌、外伤性肝破裂等肝脏疾病行手术治疗时,常常面临剩余肝缺血再灌注损伤的问题,明显增加了手术治疗的风险和影响患者术后的恢复.细胞自噬是肝脏缺血再灌注损伤后细胞程序性死亡方式之一,在动物实验模拟肝脏缺血再灌注研究时,常以检测自噬标记性分子LC3-Ⅱ的水平变化代表细胞自噬活动的强弱.现就LC3-Ⅱ在肝脏缺血再灌注损伤中的研究作一综述.     

早期反复短时缺血训练对皮瓣成活的影响及其机制研究

目的观察早期反复短时缺血训练对皮瓣成活面积、血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)及微血管密度(microvesseldensity,MVD)的影响。方法取日本大耳白兔72只,随机选取64只为实验组,在其背部两侧对称位置建立蒂在上端的皮瓣区,皮瓣范围为4cm×3cm。随机选一侧为训练皮瓣组(A组),另侧为对照皮瓣组(B组),其余8只背部两侧相同部位标记后不作处理,为空白对照组(C组)。术后即对A组皮瓣蒂部进行反复短时缺血训练。分别于术后1~8d每天随机取实验组8只断蒂,检测A、B组各时间点皮瓣成活面积;并于各时间点检测A、B组皮瓣和C组相应部位皮肤组织内的VEGF相关系数和MVD值。对A组皮瓣成活面积VEGF相关系数和MVD值行相关分折。结果术后动物全部成活,无感染、死亡,活动情况无明显变化。A组3~8d皮瓣成活面积较B组高,差异有统计学意义(P<0.05)。A、B组各时间点VEGF表达及MVD值均较C组高;A组1~6dVEGF表达高于B组,差异有统计学意义(P<0.01);且A组各时间点MVD值高于B组,差异有统计学意义(P<0.05)。相关分折见A组皮瓣成活面积与MVD、MVD与VEGF成正相关,时间点对应关系为n与n-2;相关系数分别为0.850和0.801。结论早期反复短时缺血训练可提高皮瓣成活面积,利于早期断蒂,其机制可能为训练使VEGF表达增强,进而增加皮瓣微血管密度,加速皮瓣血供重建。     

自噬相关基因在肾透明细胞癌中的表达及其临床意义

目的本研究通过对肾透明细胞癌自噬相关基因蛋白水平的检测,分析其与临床病理资料的关系。方法 Western blot检测肾透明细胞癌中自噬相关基因LC3和Beclin1的蛋白表达量。结果 Western blot检测显示肾透明细胞癌中自噬相关基因LC3和Beclin1的蛋白表达水平均低于癌旁组织组(P0.05);低分化组和中分化组LC3的蛋白表达水平比高分化组低(P0.05);进展期和转移性肾癌组比局限性肾癌组LC3的蛋白表达水平低(P0.05)。结论自噬在肾透明细胞癌中的低表达水平可能与肾透明细胞癌的发生、发展及转移有关。     

局部应用重组水蛭素对家兔耳静脉淤血皮瓣成活的影响

目的 观察局部应用重组水蛭素对家兔耳静脉淤血皮瓣成活的影响.方法 选取健康普通大耳白兔18只,按照随机数字表法分为对照组、低分子肝素治疗组、重组水蛭素治疗组,每组6只.各组家兔麻醉后在左耳背制作静脉淤血皮瓣模型:皮瓣大小为6 cm×3 cm,以耳中心动脉为惟一血供、1 cm宽蒂部为惟一静脉回流途径.术后分别于皮瓣下多点均匀注射 1 mL生理盐水、低分子肝素(625 U)、重组水蛭素(1 U),皮瓣原位缝合.观察皮瓣外观并计算成活率;术后1、3、5、7 d 取皮瓣远端组织检测血栓素B2含量.对数据行单因素方差分析、t检验.结果 各组家兔皮瓣完全坏死区域毛发脱落明显;术后皮瓣均肿胀明显,远端淤血形成,对照组颜色明显深于2个治疗组.术后1 d 重组水蛭素治疗组1只家兔、低分子肝素治疗组2只家兔、对照组4只家兔出现明显血肿.低分子肝素治疗组、重组水蛭素治疗组家兔皮瓣成活率分别为(92.3±1.7)%、(94.8±1.9)%,均高于对照组[(77.9±1.2)%,F=191.29,P＜0.05].2个治疗组家兔皮瓣成活率接近(t=2.75,P>0.05).术后3、5 d,2个治疗组家兔血栓素B2含量均明显低于对照组(t值为6.68~30.55,P值均小于0.01),而2个治疗组家兔血栓素B2含量接近(t值分别为1.22、6.44,P值均大于0.05).结论 局部应用低分子肝素或重组水蛭素,可明显改善家兔皮瓣的静脉淤血,提高皮瓣成活率.

Abstract：

Objective To observe the effect of local injection of recombinant hirudin on survival of skin flaps with venous congestion in a rabbit model. Methods Eighteen healthy rabbits were enrolled and divided into heparin-treatment (HT),recombinant hirudin treatment (RHT) and control (C) groups according to the random number table,with 6 rabbits in each group. After intravenous anesthesia with 20 g/L pentobarbital sodium,model of skin flaps with venous congestion in the size of 6 cm×3 cm was reproduced in the dorsal side of left ear of each rabbit,in which central artery of ear served as the only blood supply,and a pedicle of 1 cm in width including central vessel of ear and its accompanying nerves as the only venous return pathway. Each flap in RHT,HT,C groups was respectively given 1 mL recombinant hirudin (1 U),low-molecular-weight heparin (625 U),and isotonic saline via multi-point and homogenous injection,then they were sutured in site. Appearance and survival rate of the flaps were observed after operation. Specimens of the distal part of flaps were harvested for determination of thromboxane B2 (TXB2) on post operation day (POD) 1,3,5,7. Data were processed with one-way analysis of variance and t test. Results Rabbit model of skin flaps with venous congestion was reproduced successfully. Obvious hair loss was observed in completely necrotic parts of flap in each group. Obvious edema was observed in all flaps with venous congestion at distal site. The color of flaps in HT and RHT groups were lighter as compared with that in C group,and apparent hematoma of flap was observed in 1 rabbit of RHT group,2 rabbits of HT group,4 rabbits of C group on POD 1. The survival rate of flap in HT and RHT groups was respectively (92.3±1.7)% and (94.8±1.9)%,both higher than that in C group[(77.9±1.2)%,F=191.29,P＜0.05]. There was no statistical difference in survival rate of flap between HT group and RHT group (t=2.75,P>0.05). The content of TXB2 in HT and RHT groups on POD 3,5 was respectively lower than that in C group (with t value from 6.68 to 30.55,P values all below 0.01),but there was no statistical difference between HT and RHT groups (with t value respectively 1.22,6.44,P values all above 0.05). Conclusions Local injection of low-molecular-weight heparin or recombinant hirudin can significantly ameliorate venous congestion of skin flap in rabbit ear,and improve its survival rate.     

重组水蛭素对大鼠撕脱皮瓣存活的影响

目的 探讨重组水蛭素对撕脱皮瓣的保护作用及其在临床治疗撕脱皮瓣的应用前景.方法 将108只SD大鼠随机分为重组水蛭素组（A组）、低分子肝素组（B组）、生理盐水组（C组,对照组）,并形成撕脱皮瓣后原位缝合.术后即刻、12 h、24 h、48 h,给予皮瓣蒂部、距蒂部2 cm和4 cm3等分点皮下注射重组水蛭素、低分子肝素、生理盐水,于术后12 h、1d、3d、5d、7d,分别检测皮瓣远端组织内P选择素和血管内皮细胞生长因子（VEGF）含量,病理切片观察皮瓣远端组织毛细血管内炎性细胞聚集及微血栓形成情况,术后14d计算皮瓣存活率.结果 A组P选择素含量比B组、C组增加不明显,差异具有统计学意义（P＜0.05）,A组VEGF含量比B组、C组明显增加,差异具有统计学意义（P＜0.05）;术后14 d皮瓣存活率A组明显高于B组（P＜0.05）和C组（P＜0.01）,差异具有统计学意义.结论 局部注射重组水蛭素能有效抑制P选择素的生成,减少炎性细胞的聚集,阻断微血栓的形成,改善撕脱皮瓣的局部缺血、缺氧状态;减弱内皮细胞的损伤,促进VEGF的表达,刺激新生毛细血管增生,提高撕脱皮瓣的存活率.     

Hemoglobin-based oxygen carrier does not improve survival of ischemic rat island groin flaps.

Reducing reperfusion injury to skin flaps is an effective means to improve the survival of the flap. By enhancing oxygen delivery to the microcirculation within the flap, ischemia-reperfusion injury should be decreased, improving the flap's survival. This study evaluated the effects of a hemoglobin-based oxygen carrier (Oxyglobin) on the development of necrosis and survival of ischemic rat island groin flaps. Sprague-Dawley rats were randomly assigned to one of three treatment groups. A groin flap was elevated on each rat and subjected to 9 h of ischemia. Rats in group I were given an intravenous infusion of 0.9% saline prior to elevation of the skin flap. Rats in group II were given an intravenous infusion of Oxyglobin prior to elevation of the skin flap. Rats in group III were given a low-dose intravenous infusion of Oxyglobin following the 9 h of ischemia, just prior to reperfusion. The flaps were monitored for 7 days postoperatively for necrosis. The percentage of flap necrosis was recorded at the end of 7 days. All rats were euthanized at the completion of the study and the flaps were harvested for histopathological analysis. No significant difference was noted in the survival of the flaps or the degree of necrosis in the rats treated with Oxyglobin compared to the control group. Thus, pre-reperfusion treatment with Oxyglobin did not improve the percentage of flap survival, or the degree of severity of necrosis in rat groin flaps subjected to 9 h of ischemia.     

Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway-mediated enhancement of autophagy

Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia–reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy-related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3-methyladenine (3-MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3-MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA-induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.     

低分子右旋糖酐与盐酸罂粟碱对皮瓣成活质量影响的实验研究

目的 观察低分子右旋糖酐和盐酸罂粟碱对游离皮瓣血流通畅和成活质量的影响.方法 选用中国家兔48只,随机分为4组,每组12只.A组：对照组;B组：盐酸罂粟碱治疗组;C组：低分子右旋糖酐治疗组;D组：盐酸罂粟碱和低分子右旋糖酐联合治疗组.行兔耳游离皮瓣移植术.每只家兔术后行大体观察,组织学观察,微血管密度测定,皮瓣组织中丙二醛（malondialdehyde,MDA）检测,透射电镜观察动脉吻合口超显微结构.结果 各观察指标显示B,C,D组皆优于A组,B,D两组无明显差异,皆优于C组.结论 术中术后应用盐酸罂粟碱可有效防止血管痉挛,维持血流通畅,促进微血管生成,增强抗再灌注损伤能力,提高游离皮瓣成活质量;低分子右旋糖酐单独应用对维持游离皮瓣血流通畅和促进微血管生成等效果不明显.     

Aprotinin in Ischemia-Reperfusion injury: Flap survival and neutrophil response in a rat skin flap model

Multiple drugs have been used in experimental skin flap models to reduce the effects of reperfusion ischemia. The effects of antiproteases, however, have not been studied. A skin flap ischemia reperfusion model was developed in the rat to study the effects that aprotinin, a broad-spectrum antiserine protease, would have on skin flap viability. Thirty-two male rats underwent elevation of a ventral pedicled skin flap based on the superficial inferior epigastric artery. The flaps were subjected to 10 hr of warm ischemia by clamping the neurovascular pedicle followed by reperfusion. Aprotinin or saline (control) was administered systemically via the contralateral femoral vein either before or after the ischemic insult. Full-thickness skin biopsies were obtained at 1, 8, and 24 hr into reperfusion. Biopsies were evaluated for neutrophil concentration (using a myeloperoxidase [MPO] assay) and thromboxane B₂ [TxB₂] content. Flap survival was calculated at 1 week using standardized photography and computer-assisted digital imaging. Aprotinin given before an ischemic insult significantly improved flap survival compared to saline controls (52.3% alive vs. 29.6%, P = 0.0132, unpaired t-test). Aprotinin given after ischemia did not significantly influence flap survival (28.8% vs. 34.4% in saline controls, P = 0.708). MPO levels in the aprotinin preischemia treatment group were significantly less at 1 and 8 hr into reperfusion, indicating decreased neutrophil numbers. No statistical difference in TxB₂ levels was noted in either group at any time after reperfusion. Aprotinin significantly improves skin flap survival when given prior to but not after an ischemic insult. Aprotinin appears to lower the concentration of neutrophils in skin flaps pretreated with the drug. Reperfused skin flap levels of thromboxane B₂ are unaffected by the pre- or postischemic administration of aprotinin. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:354–361, 1998