兴奋毒性对海马脑片Ca~(2 )/CaM PK Ⅱ活性的影响

用离体孵育的大鼠海马脑片模型，研究兴奋毒性与Ｃａ２＋／ＣａＭＰＫＩＩ活性的关系。结果表明，外源性谷氨酸或ＮＭＤＡ均可抑制Ｃａ２＋／ＣａＭＰＫＩＩ的活性，此活性的抑制可被ＭＫ８０１完全拮抗，而ＤＮＱＸ却无明显拮抗作用；无胞外Ｃａ２＋时，谷氨酸导致的酶活性抑制程度不如有胞外Ｃａ２＋时显著；无胞外Ｍｇ２＋时，谷氨酸导致的酶活性抑制程度比有胞外Ｍｇ２＋时显著。结果提示兴奋毒性对Ｃａ２＋／ＣａＭＰＫＩＩ活性的抑制与ＮＭＤＡ受体介导的兴奋毒性有关     

牛磺酸抗脂质过氧化作用与调节Ca~（2＋）作用

在培养心肌细胞缺氧－再给氧模型上，发现牛磺酸（２０ｍｍｏｌ·Ｌ－１，终浓度）能显著降低细胞内脂质过氧化物（ＬＰＯ）荧光强度；剂量依赖性地提高心肌细胞超氧化物歧化酶（ＳＯＤ）活性；以荧光比率法（荧光探针为Ｉｎｄｏ－１－ＡＭ）在粘附式细胞仪（ＡＣＡＳ５７０）上测定细胞内游离Ｃａ２＋荧光比率，结果显示缺氧及再给氧后细胞内Ｃａ２＋荧光比率明显升高，２０ｍｍｏｌ·Ｌ－１牛磺酸能显著减少Ｃａ２＋荧光比率；分别以２０ｍｍｏｌ·Ｌ－１、０．４ｍｍｏｌ·Ｌ－１Ｃａ２＋及０．１ｍｍｏｌ·Ｌ－１维拉帕米处理细胞，牛磺酸能降低高Ｃａ２＋引起的细胞搏动加快；而提高低Ｃａ２＋及维拉帕米处理后的细胞搏动。提示牛磺酸对培养心肌细胞再给氧损伤有保护作用，其机理与其提高心肌细胞ＳＯＤ活性、降低细胞内游离Ｃａ２＋浓度及对细胞Ｃａ２＋双向调节作用有关。     

氧化低密度脂蛋白及辛伐他汀对人单核细胞蛋白激酶C活性和胞浆内游离钙的影响

目的探讨ＯＸ－ＬＤＬ及ＨＭＧ－ＣｏＡ还原酶抑制剂辛伐他汀对人单核细胞（Ｍｏ）表达蛋白激酶Ｃ（ＰＫＣ）活性和胞浆内游离钙（［Ｃａ２＋］ｉ）浓度的影响。方法Ｍｏ ＰＫＣ活性采用 γ－３２Ｐ－ＡＴＰ磷酸转移法,细胞内游离钙采用 Ｆｌｕｏ－３／Ａｍ荧光负载,流式细胞术检测。结果ＯＸ－ＬＤＬ呈剂量依赖方式促进人 Ｍｏ ＰＫＣ活性增加,１２ ｍｉｎ时达峰值,然后缓慢下降,２０ ｍｉｎ后仍维持较高水平,胞浆内［Ｃａ２＋］ｉ升高分２个时相,即快速相和持续相。移去细胞外液钙,ＯＸ－ＬＤＬ仍引起快速相,但持续相消失,而辛伐他汀能明显抑制ＯＸ－ＬＤＬ．引起的Ｍｏ　ＰＫＣ活性增加,并降低持续相胞浆内钙水平,而对快速相无明显影响。结论ＯＸ－ＬＤＬ能激活人单核细胞ＰＫＣ活性与升高［Ｃａ２＋］ｉ。ＯＸ－ ＬＤＬ刺激Ｍｏ［Ｃａ２＋］ｉ升高的快速相是有胞浆钙池释放引起,持续相升高主要有胞外钙内流引起。辛伐他汀抑制Ｍｏ　ＰＫＣ活性可能是通过胞内钙水平变化起作用。     

蛋白激酶C与血管平滑肌α_1肾上腺素受体触发Ca~（2＋）内流的关系

在酶新鲜分离的犬肠系膜上动脉平滑肌细胞，蛋白激酶Ｃ（ＰＫＣ）的激活剂佛波二丁酯（ＰＤＢ）引起的胞内Ｃａ２＋增高作用可被ＰＫＣ抑制剂１－（５－异喹啉磺酰）－２－甲基哌嗪（Ｈ７）所阻断，而哌唑嗪和普萘洛尔则不能阻断ＰＤＢ的这一作用；１０μｍｏｌ·Ｌ－１苯福林引起的胞内Ｃａ２＋增高作用可被１０和２０μｍｏｌ·Ｌ－１Ｈ７部分阻断；在无Ｃａ２＋液，Ｈ７可部分抑制苯福林引起的内Ｃａ２＋释放和外Ｃａ２＋内流，两者分别被抑制了３３±３％和５８±６％；ＫＣｌ（２０－１００ｍｍｏｌ·Ｌ－１）可浓度依赖性地引起胞内钙升高，这一作用可被１０和２０μｍｏｌ·Ｌ－１Ｈ７不同程度地阻断；ＰＤＢ引起的胞内Ｃａ２＋增高也可分别被１．２５和２．５μｍｏｌ·Ｌ－１维拉帕米部分和全部阻断。上述结果提示ＰＫＣ参与苯福林引起的部分内Ｃａ２＋释放和外Ｃａ２＋内流，但以参与外Ｃａ２＋内流为主；这一作用可能与ＰＫＣ激活，引起电压依赖性Ｃａ２＋通道开放有关。     

水杨酸钠对离体大鼠心脏缺血再灌损伤的影响

在离休大鼠心脏缺血再灌损伤模型上，研究水杨酸钠（ＳＡ）对缺血再灌后心功能恢复及心肌组织Ｃａ２＋含量的影响。与缺血再灌组比较，ＳＡ（０．１－１．０ｍｍｏｌ·Ｌ－１）呈剂量依赖性显著抑制心脏再灌后心功能的恢复。心肌组织Ｃａ２＋含量显著增高。络合剂ＥＤＴＡ和小牛血清白蛋白均能显著对抗ＳＡ诱导的心功能损害，使心肌组织Ｃａ２＋含量显著降低。提示ＳＡ能加重离休大鼠心脏缺血再灌损伤。其机理可能与其促进Ｃａ２＋超负荷引起的心肌损伤有关。ＥＤＴＡ和小牛血清白蛋白具有对抗ＳＡ的心肌毒性作用。     

牛磺酸对缺血大鼠心肌腺苷三磷酸酶的影响

目的观测牛磺酸（ｔａｕｒｉｎｅ，Ｔａｕ）对心肌缺血损伤时心肌肌膜和线粒体ＡＴＰ酶活性的影响。方法以异丙肾上腺素（Ｉｓｏ，５ｍｇ·ｋｇ－１）诱导心肌缺血损伤模型，用定磷法分别测定Ｃａ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶及Ｎａ＋，Ｋ＋－ＡＴＰ酶活性。结果与对照组比较，缺血组心肌肌膜和线粒体Ｃａ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶及Ｎａ＋，Ｋ＋－ＡＴＰ酶活性均降低，在注射ＩＳＰ前３０ｍｉｎ腹腔注射Ｔａｕ（２００ｍｇ·ｋｇ－１），则上述酶活性未见显著性变化。结论Ｔａｕ具有拮抗缺血大鼠心肌肌膜及线粒体Ｃａ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶及Ｎａ＋，Ｋ＋－ＡＴＰ酶活性降低的细胞保护作用     

降钙素基因相关肽对阿霉素心肌细胞毒性的保护作用

目的观察降钙素基因相关肽（ＣＧＲＰ）对阿霉素所致心肌细胞毒性作用的影响。方法采用原代培养乳鼠心肌细胞，以１０－６ｍｏｌＬ－１阿霉素造成急性心肌细胞毒性模型，ＣＧＲＰ作用浓度为１０－８ｍｏｌＬ－１。测定培养基中ＬＤＨ活性及心肌细胞内丙二醛（ＭＤＡ）、钙含量。透射电镜观察心肌细胞超微结构改变。结果阿霉素引起心肌细胞ＬＤＨ漏出明显增加；细胞内ＭＤＡ、钙含量水平明显升高；心肌细胞线粒体明显肿胀、嵴排列不整齐、断裂或消失，肌浆网明显扩张，染色质凝集。阿霉素所致心肌细胞ＬＤＨ漏出与细胞内ＭＤＡ含量水平呈正相关。ＣＧＲＰ可明显减轻阿霉素所致心肌细胞ＬＤＨ漏出及细胞内ＭＤＡ、钙的蓄积，明显减轻心肌细胞超微结构的改变。结论ＣＧＲＰ通过抑制脂质过氧化反应和减轻细胞内钙超载对阿霉素心肌细胞毒性具有保护作用     

左旋千金藤立定增强K~ 去极化对大鼠纹状体酪氨酸3-单加氧酶的激活作用(英文)

目的：研究Ｋ＋去极化对大鼠纹状体突触体酪氨酸３单加氧酶（ＴＭ）激活的机制及ＳＰＤ对此激活的影响．方法：应用ＨＰＬＣＥＣＤ法测定ＤＯＰＡ为ＴＭ的活性，并应用同位素法测定ＰＫⅡ和ＰＫＣ的活性．结果：ＳＰＤ１，１０和１００μｍｏｌ·Ｌ－１增强Ｋ＋去极化对突触体ＴＭ的活性，ＰＫＣ抑制剂ＰＭＢ１０μｍｏｌ·Ｌ－１能完全逆转Ｋ＋去极化的激活效应，而选择性Ｄ２受体激动剂ＱＰ，ＣａＭ拮抗剂Ｗ７和去除反应液中的Ｃａ２＋均不影响Ｋ＋去极化对ＴＭ的激活．Ｋ＋去极化使突触体ＰＫＣ的活性增加５３％，而对ＰＫⅡ的活性无影响．ＳＰＤ和ＱＰ均不影响Ｋ＋去极化对ＰＫＣ的激活．结论：Ｋ＋去极化对突触体ＴＭ的激活作用是由ＰＫＣ介导的，不受突触前ＤＡ自身受体的调控，但被ＳＰＤ增强．     

二甲基亚砜对原代培养大鼠肝细胞醋氨酚损伤的影响

醋氨酚（ＡＡＰ）引起肝细胞损伤时，肝细胞还原型谷胱甘肽（６ＳＨ）含量下降，胞浆游离Ｃａ２＋浓度（［Ｃａ２＋］）升高二甲亚砜（ＤＭＳＯ）对ＡＡＰ肝细胞损伤有明显的保护作用。对轻度损伤能完全拮抗，ＤＭＳＯ对ＧＳＨ含量下降有明显的拮抗作用，当ＧＳＮ维持在一定水平时，ＡＡＰ不引起［Ｃａ２＋］升高。提示ＤＭＳＯ可能通过保护ＧＳＨ等巯基物质而发挥拮抗ＡＡＰ肝细胞损伤的作用     

沙棘总黄酮对豚鼠心室乳头状肌和培养大鼠心肌细胞的电生理作用

用传统微电技术研究了沙棘总黄酮（ＴＦＨ）对心肌细胞的电生理作用。ＴＦＨ１００－２００ｍｇ．Ｌ＾－１使豚鼠心室乳头状肌ＡＰＤ缩短，收缩力下降，培养大鼠心肌细胞ＡＴＰ缩短，收缩力下降，培养大鼠心肌细胞ＡＰＤ缩短及４相除极斜率降低。ＴＦＨ１００ｍｇ．Ｌ＾－１可抑制毒毛花甙Ｇ诱发豚鼠乳头状肌心律失常。提示，上述作用主要与ＴＦＨ抑制心肌细胞Ｃａ＾２＋内流影响心肌细胞内Ｃａ＾２＋储库有关。     

牛磺酸对肢体缺血再灌注致多器官损伤的预防作用研究

目的探讨牛磺酸在肢体缺血再灌注致多器官损伤的预防作用。方法（1）Wistar大鼠随机分三组：再灌注组，阻断双侧股动脉循环2h，再灌注5h；牛磺酸组，1～7d灌服20％牛磺酸3ml／只，后阻断双侧股动脉2h，再灌注5h；对照组，行假手术处理。（2）测定血白细胞总数、肝酶和心肌酶；观察红细胞SOD活性、血清谷胱甘肽（GSH）及肝、肺组织匀浆丙二醛（MDA）及器官的超微结构变化。结果再灌注组白细胞总数、心肌酶、肝酶较对照组显著降低（P〈0．05），其远隔器官超微病理示组织有弥漫性损伤。红细胞SOD及血清GSH较对照组显著下降，肝、肺组织匀浆MDA及肿瘤坏死因子含量显著增多（均P〈0．05）。而牛磺酸组病变明显改善。结论肢体缺血再灌注可激活中性粒细胞，释放氧自由基、肿瘤坏死因子，使机体处于全身炎症反应状态致远隔多器官损伤，牛磺酸可明显减轻多器官损伤。     

Protective effects of taurine against nicotine-induced oxidative damage of rat urinary bladder and kidney

Several studies demonstrate that taurine treatment prevents tissue damage in various models of inflammation. Experiments have shown that chronic nicotine administration caused oxidant damage in various organs by increasing lipid peroxidation products and decreasing the activity of endogenous antioxidants. The aim of this study was to investigate the effects of taurine treatment on nicotine-induced oxidative changes in rat urinary bladder and kidney and to explore the possible mechanisms of action. Male Wistar albino rats were injected with nicotine hydrogen bitartrate (0.6 mg/kg i.p.) or saline for 21 days. Taurine was administered (50 mg/kg i.p.) alone or along with nicotine injections. At the end of the treatment period bladder tissue was used for in vitro contractility studies, or stored along with kidney tissue for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Tissue samples were also examined histologically. Serum samples were stored for the measurement of MDA, GSH, blood urea nitrogen, creatinine and lactate dehydrogenase activity. Chronic nicotine treatment decreased the contractile activity of the bladder strips to carbachol and increased lipid peroxidation, MPO levels and tissue collagen content of the bladder and kidney samples. Taurine supplementation to nicotine-treated animals reversed the contractile dysfunction of the bladder strips. It also preserved the renal functions, restored the endogenous GSH levels and decreased high lipid peroxidation and MPO activities in both urinary bladder and kidney tissues. These data suggest that taurine supplementation effectively counteracts the deleterious effect of chronic nicotine administration on bladder and kidney functions and attenuates oxidative damage possibly by its antioxidant effects.     

Effects of taurine on cerulein-induced acute pancreatitis in the rat.

Taurine, or 2-aminoethane sulfonic acid, is an intracellular amino acid and has been suggested to have a function in protecting biological systems from oxidative tissue damage. The aim of this study was to determine the effect of taurine against cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by administering three subcutaneous injections of cerulein (40 microg/kg body weight) at 1-hour intervals, while taurine was administered intravenously at graded doses (30, 100, or 300 mg/kg, respectively) following the first cerulein injection. The severities of pancreatitis and lung injury were determined by measuring biochemical parameters, tissue myeloperoxidase (MPO), and histological changes. To clarify the mechanism of taurine, serum IL-1beta and TNF-alpha levels and tissue concentrations of malondialdehyde (MDA) were evaluated. In cerulein-induced acute edematous pancreatitis, treatment with taurine significantly decreased hyperamylasemia, tissue MPO, pancreatic edema, and the extent of pancreatic and pulmonary injury. Taurine decreased MDA concentration in the pancreas and lung, but not the serum cytokine concentration. We would conclude that taurine has beneficial effects in cerulein-induced acute pancreatitis and lung injuries by preventing the production of oxygen free radicals.     

Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats

The therapeutic usefulness of doxorubicin (DXR), an anthracycline antibiotic, is limited by its cardiotoxicity. The present study investigated the effects of telmisartan, an angiotensin II receptor (AT1) antagonist against doxorubicin-induced cardiotoxicity in rats using biochemical and histopathological approaches. Doxorubicin (20 mg/kg) was injected intraperitoneally (ip) as a single dose and telmisartan (10 mg/kg) was administered orally for 7 days. Rats treated with DXR showed cardiotoxicity as evidenced by elevation of serum lactate dehydrogenase (LDH) activity, tissue malondialdehyde (MDA) level, catalase activity and a decrease in the level of glutathione (GSH). Pre- and post-treatment with telmisartan elicited a significant decrease in the activities of LDH and catalase in comparison with DXR-treated group. Furthermore, pretreatment with telmisartan also decreased lipid peroxidation (MDA level) and increased the GSH content in comparison with DXR group. However, the difference in lipid peroxidation and GSH content were not statistically significant in post-treated group. Histopathological studies showed disruption of cardiac tisuues in DXR groups. Pre- and post-treatment with telmisartan reduced the damage of cardiac tissue in rats. These results suggest that telmisartan treatment provides a significant protective effect against acute-doxorubicin induced cardiotoxicity in rats.     

牛磺酸对大鼠心肌缺血损伤的保护

采用大鼠皮下注射异丙肾上腺素（ＩＳＰ，５ｍｇ·ｋｇ－１）造成心肌缺血损伤模型。观测心肌线粒体（Ｍｉｔ）、丙二醛（ＭＤＡ）、总磷脂（ＰＬ）、胆固醇（ＣＨ）含量，超氧化物歧化酶（ＳＯＤ）和谷胱甘肽过氧化物酶（ＧＳＨ·Ｐｘ）活力及心肌钙含量的变化。结果发现：在注射ＩＳＰ前３０ｍｉｎ腹腔注射牛磺酸（Ｔａｕ，２００ｍｇ·ｋｇ－１），对心肌缺血损伤有保护作用，表现为能明显减少心肌Ｍｉｔ中ＭＤＡ的生成，提高ＳＯＤ和ＧＳＨ·Ｐｘ）活力，减轻磷脂的降解和心肌钙聚集作用。提示：Ｔａｕ对心肌Ｍｉｔ的保护作用可能是其抗心肌缺血损伤的重要机制之一。     

牛磺酸对大鼠视网膜缺血再灌注损伤的影响

目的观察牛磺酸对大鼠视网膜缺血再灌注损伤（retinal ischemia-reperfusion，RIR）的影响及其作用机制。方法将120只大鼠随机分为3组：对照组、缺血组、保护组，采用前房灌注液体形成14．63kPa高眼压1h的方法，建立RIR模型，连续3d，2次／d，腹腔注射10％的牛磺酸，剂量为100mg／kg，于手术前30min加注1次。对照组给予同等剂量的生理盐水。两组缺血60min后，分别再灌注0、2、6、12、24、48、72h用比色法进行视网膜SOD、MDA、NO的测定；用光镜测量包埋切片的平均视网膜内层厚度（meanthicknessofinnerretinallayer，MTIRL）。结果牛磺酸能显著对抗大鼠视网膜缺血再灌注后MDA和NO水平的升高，同时能改善平均视网膜内层厚度的变化，但对SOD的作用不确定。结论牛磺酸可减轻大鼠视网膜缺血再灌注后的损伤。     

Taurine and calcium interaction in protection of myocardium exposed to ischemic reperfusion injury.

We aimed to investigate the cardio-protective role of taurine with low calcium level against reperfusion damage by adding taurine to extracellular fluid. Guinea-pig hearts were mounted on Langendorf perfusion apparatus and different compositions of perfusion solutions were prepared for each experimental group. After 20 min of normothermic ischemia the hearts were reperfused. Pre-ischemic, post-ischemic and post-reperfusion percentage changes of heart rate and contractile force were compared. Post-reperfusion tissue weight, malondialdehyde (MDA) and prostaglandin E-like activity (PGE-like activity) were assessed. Taurine-added low-calcium perfusion solution significantly decreased the postischemic myocardial injury.     

Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin

AIM: To investigate the effects of deferiprone on doxorubicin-induced cardiotoxicity and determine its protection on cardiac contractility in vivo at tissue level. METHODS: Spontaneously-beating isolated atria from rats were pretreated with deferiprone for 10 min at 1.2 mmol/L or 0.3 mmol/L, respectively before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min. Contractility (dF/dt) was assessed every 10 min during the incubation. After that, the tissues around the sinuatrial nodes were fixed for ultrastructural study; succinate dehydrogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD) activity, as well as malondialdehyde (MDA) level of the atria were assayed. RESULTS: Treatment with DOX alone resulted in a 49.34% reduction of the contractility, mitochondria swelling, disruption of mitochondrial crista and decreased electron density of the matrices. Conversely, with the presence of deferiprone, the negative inotropic effect and lesions in the cardiac mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity increased by 12.97%-12.11%, the MDA level decreased by 29.12%-39.82% and succinate dehydrogenase (SDH) activity was ameliorated by 25.15%-34.76%. CONCLUSION: Deferiprone can efficiently preserve cardiac contractility. Moreover, the results of this study indicate that deferiprone is able to protect mitochondrial function and structure form damage induced by DOX. This cardiac protective potential of deferiprone could be due to its defense capability against oxidative damage.     

Protective effect of taurine against doxorubicin-induced cardiotoxicity in perfused chick hearts

The ability of taurine to protect the isolated heart against doxorubicin cardiotoxicity was examined. Chick hearts perfused for 20 min with medium containing 17 microM doxorubicin exhibited a decrease in contractility, an increase in resting tension and a dramatic depletion in tissue high energy phosphate content. Addition of 20 mM taurine to the perfusate attenuated the increase in resting tension and the decrease in myocardial adenosine triphosphate content induced by doxorubicin. The present study confirms our previous in vivo observations that taurine partially prevents doxorubicin-induced cardiotoxicity.     

碱性成纤维细胞生长因子脂质体对异丙肾上腺素引起的大鼠心肌损伤的保护作用

目的考察碱性成纤维细胞生长因子(bFGF)脂质体对异丙肾上腺素(isoproterenol,ISO)引起的大鼠心肌损伤的保护作用。方法大鼠腹腔注射ISO(80 mg.kg-1)建立大鼠急性心肌损伤模型后,尾静脉注射相同剂量的bFGF水溶液、bFGF普通脂质体和bFGF长循环脂质体,48 h后取心室部分常规切片HE染色,并对血清中乳酸脱氢酶(LDH)、心肌组织中胶原(collagen)、丙二醛(MDA)及ATP酶的含量进行测定。结果bFGF水溶液给药组没有明显减轻ISO对大鼠心肌组织的损伤程度,而bFGF脂质体给药组则显著减轻了ISO引起的心肌损伤程度。bFGF普通脂质体组的LDHc、ollagen、MDA较ISO组分别降低了31.5%、24.3%、37.7%,ATP酶增加了27.9%;bFGF长循环脂质体组的LDH、collagen、MDA较ISO组分别降低了47.1%、29.7%、44.0%,ATP酶增加了32.7%。结论与相同剂量的bFGF水溶液相比bFGF脂质体对ISO引起的大鼠心肌损伤具有明显的保护作用,且长循环脂质体的效果优于普通脂质体,其原因为脂质体作为药物载体能够保护bFGF在体内的稳定性并增加其在心肌组织中的分布。