姜黄素对骨骼肌缺血再灌注损伤的保护作用及其机制研究

目的:观察姜黄素对肢体骨骼肌缺血再灌注损伤中血浆肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH)、丙二醛(MDA)含量及骨骼肌99m锝亚甲基二磷酸钠(99mTcMDP)吸收量的影响,探讨姜黄素对肢体骨骼肌缺血再灌注损伤的保护作用及其机制。方法:制作大鼠后肢缺血再灌注损伤模型,30只大鼠随机分为假手术组、对照组、干预组。分别于再灌注1 h后测定血浆CPK、LDH、MDA含量和腓肠肌99mTcMDP吸收量变化,透射电镜观察腓肠肌超微结构变化。结果:缺血再灌注对照组和姜黄素干预组与假手术组相比,血浆CPK(7296.18±1086.53,5168.49±975.39,3014.26±963.78)、LDH(1203.66±282.53,726.56±203.65,463.85±75.32)、MDA(10.36±2.65,6.78±2.12,3.54±1.89)含量明显增高(P<0.01),99mTcMDP吸收量(16.69±3.14,11.45±2.35,9.12±1.96)明显升高(P<0.01);腓肠肌超微结构损伤明显加重;姜黄素组血浆和骨骼肌的各项指标与缺血再灌注对照组相比显著降低(P<0.01),腓肠肌超微结构损伤明显减轻。结论:姜黄素能有效降低血浆CPK、LDH、MDA含量,减少骨骼肌99mTcMDP吸收量,减轻缺血再灌注骨骼肌坏死程度和坏死范围,改善骨骼肌再灌注损伤的超微结构,说明姜黄素对骨骼肌缺血再灌注损伤具有明显的保护作用。     

骨骼肌缺血再灌注损伤血管机制及防治作用的研究进展

骨骼肌缺血再灌注损伤是由复杂的多因素引起的血液回流受阻导致组织功能障碍,是骨科临床常见的手术并发症。尽管造成此现象的原因尚未完全明了,但血管功能障碍起主要作用。H2O2是引起血管损伤的重要因素。本文主要针对骨骼肌缺血再灌注损伤的血管机制的研究及防治进展加以综述。     

异搏定灌注对断肢骨骼肌保护作用的实验研究

观察异搏定对断肢骨骼肌，血管平滑肌细胞的超微结构，和对骨骼肌中Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶，Ｃａ＾２＋－ＡＴＰ酶活性的保护作用。方法；大鼠后肢断离后，用含０．０５ｍｇ／ｍｌ异搏定的林格氏液５ｍｌ灌注，以林格氏液灌注的断肢为对照组。结果；缺血损伤引起的肌质网扩张，线粒体肿胀，核染色质凝聚现象出现的时间，在异博定灌注组比对照约晚８小时。     

缺血后处理对骨骼肌缺血再灌注后肺损伤保护作用的机制

目的：探讨缺血后处理（I-postC）对大鼠双侧后肢骨骼肌缺血再灌注（I/R）后肺损伤的保护作用及机制。方法：阻断肾下腹主动脉建立大鼠双侧后肢骨骼肌I/R损伤模型。48只大鼠随机分为3组：I/R组、缺血预处理（IPC）组及I-postC组,每组16只。分别于再灌注后12、24h各处死8只,取肺组织标本,观察肺组织形态学、湿/干重比、丙二醛（MDA）及髓过氧化物酶（MPO）的变化。原位杂交和RT-PCR方法检测肺组织中细胞间黏附分子（ICAM）-1mRNA的表达,Western blot检测ICAM-1蛋白表达。结果：再灌注12或24h后I/R组有明显的弥散功能障碍,表现为间质浸润细胞增多并伴有明显水肿。IPC组和I-postC组的各项指标均较I/R组明显降低,差异有统计学意义（P〈0.01）,但2组之间差异无统计学意义（P〉0.05）。结论：I-postC可以减轻大鼠双侧后肢骨骼肌I/R后肺损伤,与IPC可能存在共同的作用机制。     

心脏营养素-1对失神经骨骼肌的营养和保护作用

目的探讨心脏营养素-1（Cardiotrophin-1，CT-1）及其受体在失神经骨骼肌中的表达规律，观察外源性CT-1对失神经骨骼肌的营养和保护作用。方法选用11组Swiss小鼠，每组10只，切断其右侧胫神经，分别于术后不同时间点完整切取失神经腓肠肌，用Northern blot法测定肌肉中CT-1及其受体亚基LIFR-β，gp130的mRNA含量，探讨三者的表达规律。另取Swiss小鼠30只，同样方法切断其胫神经后，连续腹腔注射CT-1（100μg／kg／d），于7、14和28d后检测失神经腓肠肌的湿重、肌纤维横截面积和肌肉总蛋白含量，观察超微结构的变化，分别与对照组比较。结果CT-1及其受体在正常骨骼肌中均有表达。胫神经切断后，腓肠肌中CT-1的表达进行性下降；而LIFR-β和gp130在早期均有一个表达增高的过程，前者的表达高峰出现在失神经支配后24h，后者在神经切断后1周表达最高。连续应用外源性CT-12周，有效地维持了失神经腓肠肌的湿重、肌纤维横截面积和总蛋白含量，减轻了肌浆网的扩张程度。用药4周后，这种效果更加明显。结论内源性CT-1表达不足，是失神经骨骼肌早期萎缩的一个重要因素。受体gp130／LIFR-β的表达上调，提高了肌肉对其配体CT-1的敏感性，及时应用外源性CT-1，可对失神经骨骼肌产生营养和保护作用，能有效地延缓失神经骨骼肌的萎缩。     

牛磺酸对反复力竭运动大鼠骨骼肌线粒体的保护作用

目的 探讨牛磺酸对反复力竭运动大鼠骨骼肌线粒体的保护作用.方法 雄性SD大鼠30只随机分为安静对照组、力竭对照组、牛磺酸组,每组10只.安静对照组和力竭对照组大鼠每天按0.8 mL/kg灌喂生理盐水1次;牛磺酸组大鼠每天用200 mg/L牛磺酸按200 mg/kg灌喂1次.力竭对照组和牛磺酸组大鼠运动前先连续灌喂15d,力竭运动期间(30 d)每天继续灌喂.安静对照组大鼠整个实验过程中不运动,只灌喂生理盐水,灌喂时间与力竭对照组和牛磺酸组一样,共45 d.运动后,处死大鼠,切取股四头肌,并对大鼠体质量及股四头肌湿重进行比较;行透射电镜观察,着重观察股四头肌线粒体形态.结果 力竭对照组体质量、股四头肌湿重显著低于安静对照组和牛磺酸组,力竭对照组大鼠骨骼肌肌丝排列紊乱,线粒体肿胀和空泡变性,牛磺酸组大部分骨骼肌超微结构图接近正常.结论 口服牛磺酸对反复力竭运动大鼠骨骼肌线粒体具有保护作用,它减少反复力竭收缩骨骼肌的坏死丢失.     

不同灌注液对人离体小动脉保护作用的超微观察

目的 研究不同灌注液对离体小动脉超微结构的影响.方法 对手指近端毁损伤,缺乏再植条件或患者放弃再植的18指近节离断手指(热缺血时间＜2 h),分成3组,每组6指,分别在指动脉内灌注能量合剂(A组)、肝素钠+1%利多卡因(B组)和生理盐水(C组),4℃保存.分别于灌注后2、4 6 8、12、16、24 h切取指动脉3 mm,固定后切片电镜下观察小动脉在不同时间段超微结构的变化.另取离断指体近端未缺血的健康指动脉3 mm直接固定,为对照组.结果 电镜下观察:A组灌注8 h后,小动脉平滑肌细胞线粒体仅轻度肿胀,嵴变短.B组灌注4 h后,线粒体明显肿胀和内质网扩张;8 h后,血管平滑肌细胞内线粒体进一步肿大,嵴稀疏.C组灌注2 h后,内皮细胞轻度肿胀,少数脱落;4 h后,内皮细胞肿胀,部分脱落,血管平滑肌细胞内线粒体开始肿大;8 h后,血管平滑肌细胞内线粒体进一步肿大,部分出现空泡,嵴减少,基质变淡.与A组和C组比较,小动脉经肝素钠+利多卡因灌注后内皮细胞脱落延迟至16 h.结论 能量合剂灌注液对离体小动脉的超微结构有保护作用,能够减轻肢体缺血再灌注损伤的程度.     

感觉神经(元)对失神经骨骼肌超微结构保护作用的实验研究

目的观察感觉神经（元）对失神经骨骼肌超微结构的保护作用。方法60只SD大鼠,按手术先后顺序随机分成10组,每组6只。A组(对照组)肱二头肌完全失神经支配。B～E组(实验组)B组为失神经支配加感觉神经种植组,C组为失神经支配加感觉神经寄养组,D组为失神经支配加背根神经节种植组,E组为节前撕脱的感觉神经种植组。术后1、3个月取材,各组又分为二个时间组。用透射电镜观察肌肉超微结构的变化。结果与对照组相比,各实验组肌肉退变核数少、线粒体肿胀及肌质网扩张程度轻、毛细血管/肌纤维数比值大、间质胶原纤维和成纤维细胞少、肌丝肌节排列整齐。结论感觉神经（元）对失神经骨骼肌超微结构有保护作用。     

缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响

目的 探讨缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响以及应用缺血后处理的时机.方法 将32只大鼠随机分成四组,采用切断患肢全部皮肤、肌肉和神经,保留患肢股动静脉的动物模型,通过夹闭和开放股动静脉造成骨骼肌缺血和再灌注损伤.采用测定骨骼肌缺血4 h.再灌注1 h后血清丙二醛(MDA)、骨骼肌髓过氧化物酶(MPO),再灌注6 h后骨骼肌的死亡程度来观察缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响,以及再灌注5 min后应用缺血后处理是否对骨骼肌缺血再灌注损伤有保护作用.结果 对骨骼肌缺血4 h再灌注6 h的损伤,再灌注开始后即刻应用30 s缺血、30 s再通,三次循环的缺血后处理对骨骼肌的缺血再灌注损伤即有保护作用,不仅减少了骨骼肌再灌注区域中性粒细胞浸润(MPO)和血清氧自由基水平(MDA)水平,而且减少了骨骼肌的死亡程度;再灌注5 min后应用缺血后处理并没有降低骨骼肌缺血再灌注区域的MPO和血清MDA水平,也没有降低骨骼肌缺血再灌注后的死亡程度,与直接缺血再灌注组相同,对骨骼肌缺血再灌注损伤并没有保护作用.结论 骨骼肌缺血后再灌注开始前立刻应用缺血后处理对大鼠骨骼肌缺血再灌注损伤有一定的保护效果,可以减少骨骼肌缺血再灌注损伤后的死亡程度;缺血后处理应用时机非常重要,再灌注5 min后应用缺血后处理则失去对骨骼肌缺血再灌注损伤的保护作用.     

超氧化物歧化酶对大鼠肝脏缺血再灌注损伤保护作用的体外实验

目的：探讨氧自由基清除剂对大鼠肝脏缺血再灌注损伤的保护作用及其机理。方法：将Wistar大鼠分成三组，各组通过门静脉插管，对肝脏进行原位灌洗，心脏搏动组以4℃HTK液灌洗；心脏停跳组在心脏搏动停止60min后，以同样方法灌洗肝脏；SOD实验组灌洗方法同心脏停跳组，但灌洗液中含有超氧化物歧化酶（SOD）7500IU。灌注结束后，快速切取肝脏，于4℃HTK液中保存24h，然后在体外以Krebs-Henseleit缓冲液再灌注45min。测定再灌注过程中的门静脉压力，收集再灌注液，进行血气分析，测定其中丙氨酸转氨酶（ALT）、谷氨酸乳酸脱氢酶（GLDH）及脂质过氧化物（LPO）的含量；切取肝组织，检测其能量底物总和（TAN）及细胞凋亡情况。结果：再灌注期间，SOD实验组的门静脉压力为（6．4±0．9）cmH20，明显低于心脏停跳组的（12．1±0．7）cmH20（P〈0．01）。随着再灌注时间的延长，灌注液中AL]r和GLDH的浓度不断升高，但SOD实验组明显低于心脏停跳组（P〈0．05）。心脏停跳组肝脏氧消耗量明显低于心脏搏动组（P〈0．01），而SOD实验组氧消耗量明显增加（P〈0．01）。SOD实验组的TAN为（7．6±0．4）μmol／g，明显高于心脏停跳组的（5．3±0．7）,μmol／g（P＜0．05）。SOD实验组灌注液中LPO的含量为（0．42±0．10）nmol／g，明显低于心脏停跳组的（0．98±0．18）nmol／g（P＜0．01）。心脏搏动组只有极少量的肝窦内皮细胞和肝细胞凋亡，SOD实验组中凋亡细胞的数量也非常有限，而在心脏停跳组，则有大量的肝窦内皮细胞发生凋亡。结论：在体外，SOD能显著减轻大鼠肝脏的缺血再灌注损伤，这可能与SOD抑制了氧自由基所致的细胞凋亡有关。     

Study on the relationship between endometrial carcinoma and serum levels of malondialdehyde and superoxide dismutase

Objective:To study the relationship of human endometrial carcinoma and the serum levels of malondialdehyde and superoxide dismutase.Methods:The serum levels of malondialdehyde(MDA),total superoxide dismutase(T-SOD),CuZn-superox-ide dismutase(CuZn-SOD),Mn-superoxide dismutase(Mn-SOD)were measured in 37 women with endometrlal carcinoma(study group)and 40 healthy women(control group).The relationship between surgical-pathological smiling of the tumor and these parameters was analyzed.Results:(1)The serum levels of MDA were significantly higher in study group than in control group(P<0.01);(2)The levels of T-SOD,CuZn-SOD were significantly lower in study group than in control group(P<0.01,P<0.01,respectively),while the levels of Mn-SOD were slightly lower in study group but there was no statistical difference(P>0.05);(3)There was a positive correlation between surgical-patholological staging and the level of MDA(r=0.9206,P<0.01),and a negative correlation between surgical-pethological staging and the level of T-SOD(r=-0.9210,P<0.01)or CuZn-SOD(r=-0.9130,P<0.01)But there was no correlation between surgical-pathological staging and the level of Mn-SOD(r=-0.3970,P>0.05).Conclusion:The psthogenesis and development of endometrial carcinoma may be associated with the imbalance of oxidation and antioxidetion.     

血清微量元素和超氧歧化酶与胃癌关系的研究

目的研究胃癌患者体内血清微量元素和超氧歧化酶的变化关系。方法对胃癌、消化性溃疡、慢性胃炎患者和正常人(对照组)进行血清6种微量元素和超氧歧化酶的测定。结果胃癌组镁(Mg)、钙(Ca)、铜(Cu)和超氧歧化酶(SOD)明显低于对照组,分别为Mg(0.71±0.14)mmol/L与(0.91±0.25)mmol/L相比,P=0.001;Ca(1.71±0.26)mmol/L与(1.98±0.28)mmol/L相比,P=0.001;Cu(12.7±5.5)μmol/L与(16.2±3.3)μmol/L相比,P=0.038;SOD(6.67±0.96)nU/ml与(7.85±1.10)nU/ml相比,P=0.003。而慢性胃炎组的微量元素和SOD与对照组相比,差异无显著性意义。结论血清微量元素和SOD可能与胃癌的发生有关。     

A lecithinized superoxide dismutase (PC‐SOD) improves ulcerative colitis

Objective To assess the safety and efficacy of lecithinized superoxide dismutase (PC‐SOD) in patients with ulcerative colitis (UC). Method PC‐SOD was injected once daily at doses of 40 mg (n = 22) and 80 mg (n = 20) for a total treatment period of 4 weeks. Efficacy was assessed by UC‐Disease Activity Index (DAI) total score. All side effects were recorded and investigated. Results At 4 weeks, the UC‐DAI total score was significantly decreased vs baseline in both the 40 mg and 80 mg groups. It was confirmed that PC‐SOD 80 mg was, at least, not significantly superior to PC‐SOD 40 mg. Twenty incidences of side effects were noted in 12 (54.55%) of 22 patients in the 40 mg group, while there were three incidences of side effects in two (10.00%) of 20 patients in the 80 mg group. None of these side effects was severe. Thus it was concluded that the test drug is safe when given at daily dosages of 40 mg and 80 mg. Conclusion In this pilot study PC‐SOD improved UC more rapidly than previously existing drugs. A double blind, placebo‐controlled clinical trial of PC‐SOD 40 mg/day is required to confirm the efficacy of this agent against UC.     

缺血预处理改善骨骼肌功能的研究

目的：探讨缺血预处理法改善缺血骨骼肌功能的临床价值。方法：用ＳＤ大鼠１２只，以右后肢为动物实验模型。分为缺血组（对照组，鼠６只），即缺血４小时后再灌注１小时的方法；缺血预处理组（实验组，鼠６只），缺血过程同对照组，但在缺血前预先经过２次缺血５分钟、再灌注１０分钟的处理。实验时，分别于缺血前、缺血１、４小时及再灌注１小时时，测定两组实验侧肢体腓肠肌最大肌张力的变化。实验结束后分别测量血ＭＤＡ、ＣＰＫ及大鼠右后肢９９ｍＴｃ亚甲基二磷酸计数。结果：实验组最大肌张力的变化（缺血４小时、再灌注１小时时）较对照组有明显改善；血ＭＤＡ、ＣＰＫ及肌肉９９ｍＴｃ亚甲基二磷酸较对照组显著降低。结论：缺血预处理不仅能改善骨骼肌的缺血耐受性，而且能有效地改善骨骼肌的功能     

缺血对兔血管平滑肌的损伤作用

研究兔断肢血管平滑肌组织中钙、镁离子含量及线粒体形态的变化与术后血循环危象的关系。方法:用原子吸收光谱分光光度计测定血管平滑肌组织中钙、镁离子的含量。用图像分析仪定量分析线粒体的结构变化。结果:缺血时间超过8小时,血管平滑肌组织中钙离子含量明显升高(P<0.01);线粒体明显受损。结论:血管平滑肌组织中钙离子增高在血循危象的发生中起着重要作用。     

Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits

Involvement of the superoxide radical in impaired relaxation of penile cavernous smooth muscle in hypercholesterolemia was investigated. New Zealand White rabbits (n = 40) were randomly divided into control and treatment groups. The control group (n = 20) received a regular diet while the treatment group (n = 20) was fed a diet of 2% cholesterol for 8 weeks. Blood level of cholesterol in the cholesterol-fed group was significantly higher than that of the control group. The contraction responses of cavernous tissues to norepinephrine were not significantly different in the two groups. The relaxation responses to endothelium-dependent agents (acetylcholine, bradykinin) were significantly reduced in the hypercholesterolemic group compared with the control group. However, the relaxation responses to endothelium-independent agents (papaverine, verapamil) were not significantly different in the two groups. The production of superoxide radicals was significantly higher in the hypercholesterolemic group than in the control group (P < 0.01). The activity of superoxide dismutase (total SOD, Mn-SOD, Cu,ZnSOD) increased significantly in the hypercholesterolemic group compared with the control group (P < 0.05). The activities of catalase and glutathione peroxidase also increased in the hypercholesterolemic group, but were not significantly higher than those of the control group. Therefore, production of the superoxide radicals in rabbit cavernous tissues increases in the state of hypercholesterolemia, which may lead to functional impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli.     

Orgotein (superoxide dismutase): A drug for the amelioration of radiation-induced side effects

Summary Orgotein, the drug version of Cu-Zn superoxide dismutases is a new and safe anti-inflammatory agent. Animal experiments have shown that it does not interfere with the tumourolytic effects of radiation or chemotherapy. A double-blind, placebo-controlled study has demonstrated that orgotein injected after each daily irradiation session can be used safely and effectively to ameliorate or prevent the side effects due to high-energy radiation therapy (8,400 or 6,400 rads) of bladder tumours. Orgotein significantly reduced the signs and symptoms both in the bladder and the bowel, indicating that it provides a therapeutic regimen for control of these side effects, which to date could only be treated symptomatically.