地塞米松减轻皮瓣缺血再灌注损伤的实验研究

皮瓣修复创面，常伴随缺血－再灌注损伤，影响了皮瓣的成活。其发病机制复杂，目前有不少处理方法，但效果常不满意。地塞米松对其防治作用，目前尚少见报道。本文以地塞米松防治皮瓣缺血－再灌注损伤，取得了满意效果。材料与方法取健康Ｗｉｓｔａｒ大鼠（２５０～３００...     

缺血预处理对大鼠小肠缺血再灌注损伤的作用

目的 了解缺血预处理（ＩＰ）对小肠缺血的作用。方法 在不同缺血预处理的大鼠模型上，观察缺血再灌注后肠组织腺苷酸含量和肠粘膜损伤情况。结果 ＩＰ１组（预处理：１０分钟缺血１５分钟再灌注和ＩＰ２组（３分钟缺血５分钟再灌接以７分种１０分钟再灌）小肠的ＡＴＰ和总腺苷酸含量较对照组明显增高，肠粘膜损伤亦明显减轻（Ｐ〈０．０５）。．结论 ＩＰ１和ＩＰ２组的缺血预处理对小肠缺知再灌注损伤有一定的保护作用。     

地塞米松减轻皮瓣缺血-再灌注损伤所引起的全身损伤性反应

目的：研究皮瓣缺血-再灌注损伤所引起的机体全身损伤性反应，阐明其机理及地塞米松的保护性作用。方法：将大鼠分为皮瓣原位缝合组(Ⅰ组)，生理盐水对照组(Ⅱ组)，地塞米松治疗组(Ⅲ组)。观察耳部微循环，肺、肠、耳部血管组织学改变。测量全血中性粒细胞凋亡率、死亡率，血浆TNFα，IL-10浓度．结果：Ⅰ组各项指标基本正常。Ⅱ组耳部微循环明显紊乱，肺、肠及耳部血管有明显组织学改变。中性粒细胞凋亡早期较少，坏死率较高。血浆TNFα于再灌注1h达到高峰，IL-10于再灌注3h达到最低。Ⅲ组耳部微循环明显改善，肺、肠及耳部血管组织学改变明显轻于Ⅱ组。中性粒细胞凋亡早期较多，坏死率较低。TNFα峰值明显低于对照组，6h即明显下降；IL-10再灌注1h达最低，3h就明显上升，其浓度明显高于对照组。结论：单纯形成皮瓣这一创伤对机体影响轻，缺血-再灌注损伤可造成肺、肠及耳部血管组织学改变，这与全身微循环紊乱；中性粒细胞凋亡与坏死过程失衡；分泌TNFα过高，IL-10过低有关。地塞米松早期应用可防治这种损伤，其作用机理是改善全身微循环，调理中性粒细胞的生命活动及平衡分泌细胞因子。     

地塞米松防治皮瓣缺血-再灌注损伤及其机制

目的研究地塞米松对中性粒细胞凋亡与坏死的调控,阐明地塞米松防治皮瓣缺血-再灌注损伤的机制. 方法 30只Wistar大鼠腹部制备3 cm×6 cm 岛状皮瓣,分成3组(n＝10).A组正常皮瓣组;B组阻断静脉8 h,腹腔注射生理盐水作为对照组;C组阻断静脉8 h,腹腔注射地塞米松5 mg/kg,作为治疗组.术后7 d观察皮瓣成活面积;以Annexin V及Propidium双标记,流式细胞仪检测全血中性粒细胞凋亡、坏死水平;电镜观察凋亡、坏死中性粒细胞的形态.并于术后1 d,从各组大鼠皮瓣中央取材,电镜观察吞噬细胞吞噬凋亡中性粒细胞形态.阻断血管前,再灌注损伤后0、 3、6、12 及 24 h,以双夹心ELISA法测量血浆肿瘤坏死因子α(tumor necrosis factor α,TNF-α)及白细胞介素10(interleukin 10,IL-10)浓度. 结果皮瓣成活面积A、C组大于B组(P<0.05),A、C组差异无统计学意义(P＞0.05).术后1、3 d,B组全血中性粒细胞凋亡含量明显低于A、C组, 6 d高于A、C组.术后1、3、6 d,中性粒细胞坏死水平B组高于A、C组.术后1 d,皮瓣中吞噬细胞吞噬凋亡中性粒细胞的数量C组明显高于B组(P<0.05).B组血浆TNF-α于再灌注1 h达到高峰,IL-10于再灌注3 h达到最低.C组TNF-α峰值明显低于B组,6 h即明显下降;IL-10再灌注1h达最低,3 h时明显上升,其浓度明显高于B组. 结论地塞米松防治皮瓣缺血再灌注损伤的机制在于调理了中性粒细胞的凋亡水平,减少了中性粒细胞的坏死数量,平衡了中性粒细胞分泌细胞因子.     

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。     

地塞米松预处理减轻肾缺血再灌注损伤

目的探讨地塞米松（dexamethasone,DEX）对小鼠肾缺血再灌注损伤的作用及其机制。方法建立小鼠肾缺血再灌注损伤模型。18只雄性C57BL／6小鼠随机分为3个组（n=6）,分别为假手术组（Sham）、肾缺血再灌注损伤模型组（IRI）和DEX预处理组。Sham和IRI组缺血前60min予生理盐水（腹腔注射）,DEX组缺血前60min给予DEX（4mg／kg）,IRI组和DEX组血管夹夹闭左侧肾蒂,置于32℃温箱后1h松开血管夹,去除右肾。Sham组操作同上,但不夹闭左侧肾蒂,再灌注24h后处死小鼠,收集血清和肾脏标本。PAS染色后观察肾脏病理形态学变化,PCR检测白细胞介素6（interleukin6,IL-6）、干扰素γ（interferonγ,IFN-γ）和肿瘤坏死因子（tumornecrosisfactorOt,TNF-a）Westernblotting检测pAkt和总的Akt。结果与Sham组相比,IRI组血清肌酐和血尿素氮明显升高。病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎症细胞浸润明显增加。PCR显示IL-6、IFN-γ和TNF-a mRNA水平明显上调,Westernblotting显示p-Akt蛋白表达量明显增加,但Akt蛋白表达量无明显差异。与IRI组相比,DEX治疗组血清肌酐、血尿素氮明显下降,肾小管上皮细胞肿胀坏死减轻、炎症细胞浸润减少,IL-6、IFN-γ和TNF-a表达降低,p-Akt表达减少,但Akt蛋白表达量无明显差异。结论DEX预处理可通过抑制Akt信号通路激活,从而抑制炎症反应,从而减轻肾缺血再灌注损伤。     

肠缺血后处理对兔缺血再灌注损伤小肠上皮细胞线粒体形态和功能的影响

目的观察缺血后处理对小肠缺血再灌注损伤的保护作用。方法30只大白兔随机分为3组，每组8只：A组，假手术组；B组，肠缺血再灌注损伤模型组；C组，肠缺血再灌注损伤模型肠缺血后处理组，实验结束后取小肠标本进行小肠上皮细胞形态和呼吸功能指标测定。结果A、C两组线粒体的数目、周长均大于B组，A、C两组问比较，A组较大（P〈0．05）。A、C两组线粒体的面积、最大直径、最小直径、等效直径均小于B组（P〈0．05），A、C两组间比较差异无统计学意义（P〉0．05）。B组线粒体的体积密度小于A组，面积密度、比表面和粒子数密度均小于其余两组（P〈0．05）。A、C两组间三维平面形态计量学各参数比较差异无统计学意义（P〉0．05）；B、C组线粒体呼吸控制比率（RCR）低于A组差异有统计学意义（P〈0．05），与C组比较，B组下降更为明显（P〈0．05）。结论小肠缺血后处理对缺血再灌注损伤肠上皮细胞线粒体形态和功能均有保护作用。     

缺血预处理减轻骨骼肌缺血再灌注损伤

目的 观察缺血预处理对骨骼肌缺血再灌注损伤的保护作用。方法 选择２４只健康兔,随机等分为实验组和对照组。实验组先进行缺血预处理,再持续阻断后肢血流４ｈ;对照组直接阻断后肢血流４ｈ,制作骨骼肌缺血再灌注损伤模型。测定再灌注期血清中肌酸磷酸激酶（ＣＰＫ）和天门冬氨酸氨基转移酶（ＡＳＴ）,镜下观察骨骼肌变化。结果 实验组血清中ＣＰＫ和ＡＳＴ的含量均明显低于对照组（Ｐ〈０．０５）。实验组骨骼肌线粒体空泡变     

肢体缺血预处理减轻肝缺血/再灌注损伤的研究进展

背景 肝缺血/再灌注损伤(hepatic ischemia/reperfusion injury,HI/RI)是肝外科手术及肝移植中常见的病理生理现象,是术后肝功能衰竭和移植物无功能的主要原因.研究表明肢体缺血预处理(limb ischemia preconditioning,LIPC)可减轻HI/RI,具体机制仍不清楚.目的 通过综述LIPC减轻HI/R1的可能机制,为临床减轻HI/RI提供新的思路.内容 介绍HI/RI机制及LIPC减轻HI/RI的可能作用机制.趋向 LIPC作为减轻HI/RI的措施具有重大的临床应用价值.     

缺血预处理对肢体缺血-再灌注损伤影响的临床观察

198 6年Ｍｕｒｒｙ等[1] 应用缺血预处理 (ｉｓｃｈｅｍｉｃ ｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ ,ＩＰＣ) ,即短时间重复缺血间断再灌注改善心肌缺血 再灌注损伤获得成功后 ,ＩＰＣ提高组织缺血耐受性的现象颇受关注[2 ] 。目前尚鲜见到骨骼肌ＩＰＣ的临床研究报道。为此 ,我们观察了ＩＰＣ改善肢体缺血 再灌注损伤的临床效果 ,现报道如下。一、对象与方法1.一般资料 :选择需气囊止血带下进行手术的患者 2 0例 ,其中男 13例 ,女7例 ,年龄 17～ 3 2岁 ,平均 2 3岁。尺桡骨骨折切开复位钢板内固定术 6例 ,半月板切除或修整术合并韧带修复术 3例…     

The Effects of Testosterone on Intestinal Ischemia/Reperfusion in Rats

ABSTRACT

Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.     

人参总皂甙对心肌缺血再灌注损伤的保护作用实验研究

应用离体作功兔心模型，研究不同浓度的人参总皂甙（ＧＳ）对心肌缺血再灌注损伤的影响。通过心肌活检电镜下线粒体记分和血流动力学指标的测定，认为人参总皂甙作为心脏停搏液的添加剂，在２０～８０ｍｇ／Ｌ的浓度范围内，具有抗心肌缺血再灌注损伤作用；并随浓度递增而增强。但当浓度达１６０ｍｇ／Ｌ时则失去上述作用，反有加重心肌缺血再灌注损伤的倾向。     

Caffeic Acid Phenethyl Ester Alleviates Mesenteric Ischemia/Reperfusion Injury

ABSTRACT

Purpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. Methods: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 μmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 μmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. Results: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). Conclusion: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.     

肠道缺血再灌注损伤时淋巴干结扎及谷氨酰胺营养干预的作用

目的研究肠道缺血再灌注损伤时肠淋巴干结扎和含谷氨酰胺的肠内营养对肠道及远隔组织的影响。方法 40只SD大鼠胃造瘘后随机分为:假手术组、普通肠内营养组、普通肠内营养+肠淋巴干结扎组、谷氨酰胺组及谷氨酰胺+肠淋巴干结扎组,每组8只。除假手术组外,其余4组大鼠行7 d肠内营养干预后开腹夹闭肠系膜上动脉60 min,2个结扎组同时进行淋巴干结扎;假手术组行普通饮食7 d后开腹60 min后关腹。所有大鼠术后继续原营养3 d。于再灌注前1 d、再灌注后1 d及3 d测定肠道通透性,在再灌注后3 d观察肠壁形态学改变,检测血清中内毒素、D-乳酸、二胺氧化酶水平及肺组织细胞凋亡指数。结果再灌注后1 d时,各组肠道通透性均比再灌注前明显增加(P0.05);再灌注后3 d时与再灌注后1 d比较,2个结扎组的肠道通透性均明显降低(P0.05)。谷氨酰胺+肠淋巴干结扎组回肠和空肠的黏膜厚度及回肠的绒毛高度明显高于其余4组(P0.05),谷氨酰胺组回肠的绒毛高度明显高于普通肠内营养组(P0.05);普通肠内营养+肠淋巴干结扎组肠壁各形态学指标均高于普通肠内营养组,但差异无统计学意义(P0.05)。肠淋巴干结扎组的肺组织细胞凋亡指数明显低于未结扎组(P0.05),内毒素、D-乳酸及二胺氧化酶水平较未结扎组有下降趋势,但差异无统计学意义(P0.05)。结论大鼠肠道缺血再灌注损伤引起肠道通透性增加、细菌内毒素移位和系统炎症反应,肠淋巴管结扎和谷氨酰胺肠内营养干预可以弱化肺组织损伤,增加肠黏膜的厚度,维护肠屏障功能,减少内毒素移位,降低血中内毒素水平,减轻系统炎症反应。含谷氨酰胺的肠内营养效果优于普通肠内营养。     

Octreotide Ameliorates Renal Ischemia/Reperfusion Injury via Antioxidation and Anti-inflammation

Oxidative stress, calcium overload, inflammation, cellular necrosis, and apoptosis are implicated in renal ischemic/reperfusion injury (RIRI). Because octreotide (OCT) is protective in retinal IRI, the effect of OCT on mouse RIRI and the mechanisms involved were investigated. The RIRI model was induced in male C57BL/6 mice, and the mice were then treated with saline or OCT. Serum and kidneys were subjected to periodic acid–Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Treatment with OCT restored the renal functions and histologic changes induced by RIRI. The administration of OCT reduced tumor necrosis factor–α and interleukin-6 levels in kidney tissues, protected the kidney from apoptosis, and significantly downregulated the expression of nuclear factor–κB p65. In addition, OCT treatment upregulated the expression of nuclear factor erythroid 2–related factor 2, heme oxygenase–1, and NAD(P)H quinone oxidoreductase 1 and enhanced the renal antioxidant capacity. These results cumulatively indicate that OCT may protect the kidneys against IRI in a mouse model through the regulation of antioxidation and anti-inflammation.     

Posttreatment with Aminoguanidine Attenuates Renal Ischemia/Reperfusion Injury in Rats

Acute renal failure secondary to ischemia/reperfusion (I/R) injury is associated with significant mortality and morbidity. Aminoguanidine (AG), an inducible nitric oxide synthase inhibitor with antioxidant properties, has been reported beneficial in renal I/R injury. The aim of the present study was to investigate the effect of AG on renal I/R injury and compare the effectiveness of different AG treatment modalities. Sprague-Dawley rats were randomly assigned to one of four groups. The control group (n?=?6) received sham operation. The I/R group (n?=?6), AG-I group (n?=?8), and AG-II group (n?=?8) received bilateral renal ischemia for 45 min followed by 24 hours of reperfusion. The AG-I group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes before the induction of ischemia. The AG-II group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes after the initiation of reperfusion. Serum urea and creatinine levels increased significantly in the I/R and AG-I groups compared to the control group. Kidney samples from rats in the I/R and AG-I groups revealed severe tubular damage at histopathological examination. Posttreatment with AG significantly reduced serum urea and creatinine levels and improved histopathological lesions compared with the I/R group. Although pretreatment with AG failed to protect kidneys against I/R injury in this experimental model, posttreatment with AG attenuated renal dysfunction and histopathological changes after I/R injury.