氯苄四氢小檗碱对小鼠缺氧大脑线粒体的保护作用

氯苄四氢小檗碱２０ｍｇ·ｋｇ－１ｉｐ３０ｍｉｎ，可以减轻小鼠缺氧后线粒体呼吸功能的下降．能提高线粒体摄氧速率和产能速率，同时降低线粒体中丙二醛含量至正常水平．结果表明氯苄四氢小檗碱对缺氧大脑线粒体具有较好的保护作用．     

马齿苋水提液对衰老模型小鼠心肌线粒体氧化损伤的保护作用

目的 :探讨马齿苋水提液对衰老模型小鼠心肌线粒体的抗氧化作用。方法 :采用小鼠注射 D-半乳糖制成衰老模型。马齿苋水提液灌胃 30 d。测定心肌线粒体内超氧化物歧化酶 (SOD) ,Ca2 + - ATP酶活性及丙二醛 (MDA)含量。结果 :马齿苋水提液能显著提高衰老模型组小鼠心肌线粒体内 SOD,Ca2 + - ATP酶活性 (P <0 .0 1) ,显著降低 MDA含量 (P <0 .0 1)。结论 :马齿苋水提液能提高衰老模型小鼠心肌线粒体的抗氧化能力 ,具有一定的抗衰老作用     

穿山龙水提物对小鼠耐缺氧及抗疲劳的作用

目的:观察穿山龙水提物对小鼠耐缺氧及抗疲劳作用的影响。方法:采用常压耐缺氧法和负重游泳法观察穿山龙水提物对小鼠耐缺氧和抗疲劳作用的影响。结果:与生理盐水组比较,穿山龙水提物治疗组能明显延长缺氧小鼠的存活时间(P<0.05或P<0.01),并能明显延长小鼠的负重游泳时间(P<0.01)。结论:穿山龙具有明显的耐缺氧及抗疲劳的作用。     

马齿苋水提物对阿尔茨海默病模型小鼠学习行为的干预作用

目的 观察马齿苋水提物对AlCl₃诱发阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠学习行为及脑组织中超氧化物歧化酶(SOD)、乙酰胆碱酯酶(Acetyl cholinesterase,AchE)活性和丙二醛(MDA)浓度的影响。方法 小鼠随机分为2批6组,正常组、模型组、吡拉西坦(3.0 g·kg^-1)组、马齿苋水提物(2.6,1.3,0.65 g·kg^-1)组。正常组口服生理盐水,AlCl₃ 200 mg·kg^-1给药制备AD小鼠模型。连续造模和口服给药40 d。使用避暗仪和水迷宫仪,检测马齿苋水提物对AD模型小鼠的学习行为的变化,测定脑组织中MDA含量、SOD和AchE活性。结果 不同浓度马齿苋水提物明显延长小鼠避暗潜伏期,减少错误次数;缩短小鼠水迷宫到达时间和减少错误次数;明显升高脑组织SOD活性,降低AchE活性和MDA含量。结论 马齿苋对AD模型小鼠学习行为具有明显的改善作用,其作用可能与升高SOD活性,降低MDA含量和AchE活性有关。     

马齿苋水提液对衰老小鼠生理机能和肝、脑形态学的影响

目的探讨马齿苋水提液对衰老小鼠的生理机能和肝、脑形态学影响.方法采用小鼠注射D-半乳糖制成衰老小鼠模型,随机将模型小鼠分为高、中、低3个质量浓度组和模型组,另设正常对照组.高、中、低质量浓度组在标准饲料基础上,每日每只分别灌喂2.5,5,10 g·mL-1马齿苋水提液0.4 mL,饲喂4周.测量各自血清超氧化物歧化酶(SOD)和丙二醛(MDA)含量,图像分析各自肝、脑形态学的改变.结果高质量浓度组SOD活性水平高于模型组,灌喂马齿苋水提液后各组MDA含量均低于模型组,衰老小鼠脑神经元数与正常对照组小鼠相比有增多趋势并存在剂量效应关系,但没有统计学差异;肝细胞核面积与核浆比均大于模型组,其中核浆比具有统计学差异.结论马齿苋水提液可能具有改善衰老小鼠生理机能和肝、脑组织形态学改变的作用,并可能具有量效关系.     

蝙蝠葛碱对实验小鼠脑缺血的保护作用

目的　研究蝙蝠葛碱 (dauricine,Dau)对小鼠缺氧及急性脑缺血再灌注所致氧化损伤及能量代谢障碍的保护作用。方法　通过常压密闭缺氧实验观察Dau对小鼠缺氧情况下存活时间的影响 ;采用酶标仪及分光光度法测定小鼠急性脑缺血再灌注后脑皮层组织和线粒体氧化损伤指标及能量代谢指标活性或含量变化。结果　①Dau延长小鼠缺氧后存活时间。②Dau改善脑缺血再灌注损伤所致脑皮层组织及线粒体SOD活性下降、MDA含量升高及线粒体GSH Px活性下降 ;改善脑皮层组织LDH及线粒体ATPase活性下降。结论　①Dau对小鼠急性缺氧具有保护作用。②Dau对脑缺血再灌注所致脑皮层组织及神经细胞线粒体氧化损伤及能量代谢障碍具保护作用     

红参水提物对Aβ_(25-35)诱导SH-SY5Y细胞凋亡的保护作用

目的 探讨红参水提物对Aβ25-35诱导人神经瘤母细胞SH-SY5Y细胞凋亡的保护作用.方法 用Aβ25-35处理SH-SY5Y细胞,模拟阿尔茨海默病患者脑内神经元的病理损伤模型,以不同浓度的红参水提物进行干预;用倒置显微镜观察其形态学的变化;MTT法测定细胞的存活率;流式细胞技术检测细胞的凋亡率以及线粒体膜电位的变化.结果 50 μmol·L-1Aβ25-35诱导SH-SY5Y细胞72 h后,细胞变圆、聚集,其存活率为39.26%土3.16%、凋亡率为37.30%±0.69%,线粒体红绿荧光强度比值为0.45±0.10;而Aβ25-35诱导的SH-SY5Y细胞与不同浓度(1、5、10 mg·ml-1)红参水提物同时孵育后,明显减少了细胞损伤,升高了细胞存活率、降低了凋亡率,并升高了线粒体红绿荧光强度比值.结论 红参水提物对Aβ25-35诱导的SH-SY5Y细胞凋亡有显著的保护作用.     

丹参水提物对乳鼠心肌细胞缺氧-复氧损伤的保护作用

本文研究丹参水提物对乳鼠心肌细胞缺氧-复氧损伤的保护作用。以乳鼠心室肌进行心肌细胞培养并建立缺氧-复氧损伤模型,检测不同浓度丹参水提物预处理后细胞的存活率,乳酸脱氢酶(LDH)、肌酸激酶(CK)、天冬氨酸转移酶(AST)的泄漏量及Akt的磷酸化水平。丹参水提物对缺氧-复氧损伤的心肌细胞具有明显的保护作用,这可能与它激活PI3K/Akt信号通路有关。     

马齿苋对去卵巢小鼠骨代谢生化指标的影响

目的 探讨马齿苋对去卵巢小鼠骨代谢生化指标的影响及其可能的机制。方法 雌性昆明小鼠采用双侧卵巢切除法建立骨质疏松小鼠模型,灌胃给予马齿苋水提取物,连续7周。记录体重、子宫、脾脏与胸腺的重量以及股骨骨重与骨长,血清钙（Ca）、磷（P）和碱性磷酸酶（ALP）水平,肝匀浆中丙二醛（MDA）和超氧化物歧化酶（SOD）水平及HE染色观察骨组织病理学。结果 与模型组相比,马齿苋水提物(WEPO)高剂量组显著抑制了卵巢切除手术(OVX)诱导的体重增加（P<0.05）、胸腺重量的增加（P<0.001）、碱性磷酸酶水平的增加（P<0.05）及显著降低了卵巢切除手术小鼠肝脏中丙二醛的水平（P<0.01）;马齿苋水提物低剂量组显著降低的卵巢切除手术小鼠血清钙的水平（P<0.05）及磷的水平（P<0.01）,且马齿苋水提物低剂量组显著增加了卵巢切除手术小鼠肝脏中超氧化物歧化酶的水平（P<0.01）;马齿苋水提物低剂量组和高剂量组均能增加卵巢切除手术小鼠子宫的重量（P<0.001）和骨长（P<0.05）;马齿苋水提物低剂量组、高剂量组对总胆固醇(TCHO)和骨重均无显著影响（P>0.05）。结论 马齿苋水提物可缓解去卵巢小鼠骨量丢失,改善骨代谢,其作用可能是通过抗氧化实现的。     

白花丹参水提物促进小鼠学习记忆作用研究

目的观察白花丹参水提物对小鼠学习记忆功能的影响。方法小鼠灌胃给予白花丹参水提物,连续1周,利用Y型迷宫,观察白花丹参水提物对正常小鼠及学习记忆障碍模型小鼠学习记忆功能的影响。结果白花丹参水提物能明显提高正常小鼠的学习能力,对由东莨菪碱所致的小鼠记忆获得障碍、亚硝酸钠所致的小鼠记忆巩固不良和三氯化铝所致急性衰老小鼠学习记忆障碍有明显改善作用。结论白花丹参水提物可促进小鼠学习记忆功能,对于防治老年痴呆具有一定意义。     

缺血再灌注损伤时脑线粒体功能的改变及姜黄素的保护作用

目的　观察缺血再灌注时脑细胞线粒体功能的改变及姜黄素对此改变的影响。方法　沙土鼠双侧颈总动脉结扎造成全脑缺血 2 0min ,再灌注 30min后取大脑半球 ,分离脑细胞线粒体。用氧电极法测定线粒体的呼吸功能及还原性辅酶Ⅰ (NADH)氧化酶、琥珀酸氧化酶和细胞色素氧化酶的活性。动物随机分为假手术组、模型对照组和姜黄素组。姜黄素 40mg·kg-1于缺血模型制作前 30minip。 结果　沙土鼠缺血后脑细胞线粒体的呼吸功能有所损伤 ,表现为呼吸控制率、磷氧比和氧化磷酸化效率均较假手术组有不同程度的降低 ,各种氧化酶的活性亦有明显下降。姜黄素组动物的这种改变明显减轻。结论　沙土鼠脑缺血再灌注后脑细胞线粒体的功能明显受损 ,而姜黄素对此损伤具有一定的保护作用。     

通心络胶囊对缺血大鼠脑细胞超微结构及线粒体呼吸功能的保护作用

目的：研究通心络胶囊对脑缺血大鼠脑细胞超微结构及脑线粒体呼吸功能的影响。方法：采用线栓法制作大鼠大脑中动脉缺血模型，透射电镜观察缺血后脑组织神经元超微结构的改变．检测线粒体内的NAD及FAD氧化呼吸链R3、R4、RCR、P／O等评价呼吸功能的指标，观察通心络（1．0、2．0mg／kg）对上述结构和指标的影响。结果：电镜照片显示通心络能改善脑组织神经元在缺血后的结构破坏情况；通心络治疗组大鼠线粒体呼吸功能明显改善。结论：通心络对缺血脑细胞有明显保护作用．机制与其能改善线粒体呼吸功能有关。     

慢性肾衰大鼠脑组织线粒体呼吸功能变化及氯沙坦的干预

目的：研究慢性肾功能衰竭（chronic renal failure,CRF）模型大鼠脑组织线粒体呼吸功能和细胞凋亡相关蛋白质的变化,并探讨氯沙坦的干预作用。方法：雄性SD大鼠24只,随机分为假手术组（Sham）、病理组（Nx）和氯沙坦干预组（Lst）,行5/6肾切除手术,建立慢性肾衰模型,Lst组于饮水中给予氯沙坦（50 mg·L-1）治疗。给药结束后,测定SCr、BUN水平及脑组织MDA的含量和SOD的活性,氧电极法检测脑组织线粒体呼吸3态氧耗率（ST3）、4态氧耗率（ST4）和呼吸控制率（RCR）,免疫印迹法观察Caspase-3、Cleaved caspase-3、Cleaved caspase-9、Bcl-2蛋白表达变化。结果：与Sham组相比,Nx组SCr、BUN含量显著升高（P<0.01）,MDA含量显著升高（P<0.01）,SOD活性显著下降（P<0.01）,ST3、RCR显著降低（P<0.01）,ST4显著升高（P<0.05）,Cleaved caspase-3、Cleaved caspase-9蛋白水平显著升高（P<0.01、P<0.05）,Caspase-3、Bcl-2蛋白水平显著降低（P<0.01）。与Nx组相比, Lst组SCr、BUN含量显著降低（P<0.01）,MDA含量显著下降（P<0.01）,ST3、RCR显著升高（P<0.01）,Cleaved caspase-3、Cleaved caspase-9蛋白水平明显降低（P<0.01）,Caspase-3、Bcl-2蛋白水平明显升高（P<0.01）。结论：慢性肾衰可造成大鼠脑组织氧化损伤,损害线粒体呼吸功能,促进神经细胞凋亡。氯沙坦通过减轻氧化应激损伤,改善线粒体呼吸功能,减少细胞凋亡,发挥神经保护作用。     

促甲状腺素释放激素对创伤休克大鼠肝线粒体呼吸功能的影响

采用大鼠单侧股骨粉碎性骨折伴15％体重失血的模型,观察动物存活率,肝脏线粒体呼吸控制率(RCR),ADP/O值的变化以及ia TRH 5 mg·kg~(-1)对肝线枉体呼吸功能的保护作用,创伤休克时,肝脏线粒体RCR,ADP/O值显著降低,24 h大鼠存活率明显减少,TRH能明显提高肝线粒体RCR,ADP/O值以及休克动物存活率,提示TRH有明显改善休克大鼠肝线粒体氧化磷酸化功能的作用。     

In vitro effect of manganese chloride exposure on reactive oxygen species generation and respiratory chain complexes activities of mitochondria isolated from rat brain.

Manganese (Mn) is known to induce mitochondrial dysfunction in excessive dose; however the mechanisms underlying its action are not elucidated clearly. To determine if Mn2+ can act directly on mitochondria or indirectly by producing reactive oxygen species (ROS), isolated mitochondria were exposed to different concentration of Mn2+ (5, 50, 500, 1000 microM). ROS generation, respiratory control ratio (RCR), mitochondrial membrane potential (MMP) and respiratory chain complexes activities were investigated. Dose-dependent inhibition of respiratory chain complexes and induction of ROS were observed; these changes were paralleled by decreasing of respiratory control ratio (RCR) both with succinate or glutamate + malate. Further investigation indicated that the membrane potential determined by Rhodamine123 release decreased after MnCl2 exposure at 1000 microM. In addition, effects of the antioxidants NAC (500 microM), GSH (500 microM) and Vitamin C (500 microM) were studied at 500 microM Mn2+. The results indicate that the effect of Mn2+ exposure on respiratory chain is not site-specific, and antioxidants can protect the mitochondria function by reducing the formation of free radicals.     

The effect of 1-(5'-oxohexyl)-3-methyl-7-propyl-xanthine on the respiratory activity of the rat brain mitochondria

The effect of 1-(5'-oxohexyl)-3-methyl-7-propyl-xanthine (HWA 285) on the respiration and oxidative phosphorylation in mitochondria isolated from normal (CM), ischemic (IsM) and postischemic (PIsM) rat brain was investigated. After the administration of 10 mg/kg HWA 285 p.o. daily for 14 days the mitochondrial ATPase activity was significantly increased, whereas O2-consumption and the respiratory control rate (RCR) were decreased. In IsM the RCR was increased, if they consumed glutamate and malate as substrates (from 3.7 +/- 0.8 to 5.0 +/- 0.75) as consequence of increased oxygen consumption in status 3. The pretreatment of the rats with 10 mg/kg HWA 285 p.o. induced a normalization of RCR in mitochondria from ischemic brains. The RCR in PIsM was apparently not influenced by HWA 285 but the oxidative phosphorylation was slightly increased. These results are consistent with the assumption that HWA 285 exerts a modulative effect on the rat brain mitochondria dependent on their functional status.     

Nicotine protects rat brain mitochondria against experimental injuries

Epidemiological studies have reported that cigarette smoking may protect from neurodegenerative diseases such as Parkinson's disease. These protective effects are thought to be mediated by nicotine. Recent data showed that nicotine significantly decreases respiratory control ratio (RCR) and superoxide anion generation of brain mitochondria. Thus, we investigated nicotine effects on rat brain in two experimental models: first, an in vitro anoxia/reoxygenation experiment and secondly, an in vivo rotenone-induced Parkinson-like syndrome. Anoxia/reoxygenation impaired mitochondrial respiration by 43.68% whereas in the presence of nicotine, it was less impaired, by 31.1% at 10(-7) M. In rats chronically administered rotenone (3 mg/kg/day), we observed profound mitochondrial damage: the RCR decreased by 50.36% and the superoxide anion generation and the membrane anisotropy increased by 56.03 and 13.43%, respectively. All of these indications of mitochondrial damage were limited by chronic administration of nicotine. Nicotine developed mitochondrial effects in vivo and in vitro at very low concentration. All these results were in accordance with epidemiological studies, which report a protective effect of nicotine in neurodegenerative diseases. Thus, we propose that one effect of nicotine is to preserve mitochondrial functions of the rat central nervous system.     

Effect of venotropic drugs on the respiratory activity of isolated mitochondria and in endothelial cells

Several drugs used in the treatment of chronic peripheral ischaemic and venous diseases, i.e. aescine, Cyclo 3, Ginkor Fort, hydroxyethylrutosides, naftidrofuryl, naphthoquinone and procyanidolic oligomers, were tested on the mitochondrial respiratory activity. The results show that all these drugs protected human endothelial cells against the hypoxia-induced decrease in ATP content. In addition, they all induced a concentration-dependent increase in respiratory control ratio (RCR) of liver mitochondria pre-incubated with the drugs for 60 min. The drugs were divided into two groups according to their effects. The first group (A), comprising aescine, Ginkor Fort, naftidrofuryl and naphthoquinone, increased RCR by decreasing state 4 respiration rate. The second group of drugs (B), comprising hydroxyethylrutosides, procyanidolic oligomers and Cyclo 3, increased RCR by increasing state 3 respiration rate. The drugs of group A were able to prevent the inhibition of complexes I and III respectively by amytal and antimycin A while the first two drugs of group B increased adenine nucleotide translocase activity. Cyclo 3 inhibited the carbonylcyanide m-chlorophenyl hydrazone (mCCP)-induced uncoupling of mitochondrial respiration. None of these seven drugs could protect complexes IV and V, respectively, from inhibition by cyanide and oligomycin. When tested on endothelial cells the drugs of group A, in contrast to group B, prevented the decrease in ATP content induced by amytal or antimycin A. The present results suggest that the protective effects on mitochondrial respiration activity by these venotropic drugs may explain their protective effect on the cellular ATP content in ischaemic conditions and some of their beneficial therapeutic effect in chronic vascular diseases.     

羌活不同提取物对小鼠脑缺血缺氧的保护作用

目的:探讨羌活不同溶剂提取物对小鼠急性脑缺血缺氧损伤的保护作用。方法:制备羌活水提取物和75%乙醇提取物,通过常压耐缺氧实验、亚硝酸钠中毒性缺氧实验,饱和氯化镁溶液致小鼠急性脑缺血实验和小鼠断头实验复制小鼠急性脑缺血缺氧模型,检测急性全脑缺血缺氧小鼠脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与正常对照组相比较:在饱和氯化镁溶液致小鼠急性脑缺血实验、常压耐缺氧实验和断头实验中各给药组小鼠的存活时间均显著延长(P<0.05,P<0.01);尼莫地平和羌活水提取物均能显著延长NaNO₂所致小鼠中毒性缺氧的存活时间(P<0.01),羌活醇提取物有延长存活时间的趋势(P>0.05);各给药组脑指数和MDA含量均显著降低(P<0.05,P<0.01),SOD活性显著增高(P<0.05,P<0.01)。结论:羌活水提取物和醇提取物对脑缺血缺氧损伤有一定的保护作用。     

Renal cortical mitochondrial dysfunction upon cadmium metallothionein administration to Sprague-Dawley rats

A bolus dose of cadmium metallothionein (CdMT) produces renal proximal tubular dysfunction because it accumulates in the tubular epithelial cells and undergoes rapid degradation, releasing Cd. Morphologically, mitochondria appear to be the target organelle. The present study examined changes in renal cortical mitochondrial function following CdMT administration and investigated whether some of these effects could be ascribed to Cd2+ accumulation in the mitochondria. Sprague-Dawley rats were injected ip with 0.3 mg Cd as CdMT/kg and the animals were sacrificed after 6, 8, or 12 h. Two- to threefold increases in urinary protein excretion and LDH activity were evident at 8 h, with marked elevations (11- and 29-fold) thereafter. Renal cortical mitochondria were swollen and rounded at 12 h. The mitochondrial Cd level was 399 pmol/mg protein at 6 h and did not change significantly during the next 6 h; however, mitochondrial respiratory function declined with time. At 12 h, state 3 oxygen consumption, respiratory control ratio (RCR), and ADP:O (P/O) ratio were 48, 49, and 76% of control values, respectively, indicating inhibition of electron transfer and oxidative phosphorylation. The direct effect of Cd on mitochondrial function was examined by incubating mitochondria from untreated rats with 0.1-2 microM CdCl2. Rapid uptake of Cd resulted in concentration-dependent effects on respiration. After 1 min of incubation with 2 microM Cd, the mitochondria contained 262 microgCd/mg protein and state 3 respiration and RCR values were 75 and 33% of control levels, respectively. Thus, renal proximal tubular cell damage following a bolus dose of CdMT involves perturbations in mitochondrial respiration, brought on by the accumulation of Cd.