阿托伐他汀对急性缺血心肌细胞的保护作用

目的探讨不同剂量的阿托伐他汀预处理对大鼠急性缺血心肌细胞保护作用及其机制。方法雄性SD大鼠40只,随机分为阿托伐他汀高剂量组(20 mg.kg-1.d-1),中剂量组(10 mg.kg-1.d-1),低剂量组(2 mg.kg-1.d-1),对照组(等量生理盐水),每组10只。伊文蓝和TTC染色法确定缺血和梗死心肌的范围;比色法测定心肌组织内的髓过氧化物酶(MPO)、心肌内NO活性;酶动力法测定肌酸激酶同工酶(CK-MB)的活性。结果与对照组比较,阿托伐他汀高、中剂量组可明显减少心肌梗死面积,明显降低CK-MB和心肌内的MPO水平(P<0.01);显著增加心肌内的NO水平(P<0.05)。阿托伐他汀高、中、低剂量组间无明显差异(P>0.05)。结论高、中剂量的阿托伐他汀对急性缺血心肌细胞具有保护作用,机制可能与NO有关。     

阿托伐他汀对大鼠胰岛功能影响的量效和时效关系

目的 观察阿托伐他汀对Wistar大鼠胰岛功能及糖耐量的影响,研究其效应与剂量、时间的相关性.方法 将60只8周龄正常Wistar大鼠采用随机数字表法分为正常对照组(生理盐水2 ml/d,n=10)、低剂量阿托伐他汀组(阿托伐他汀5 mg· kg-1·d-1,n=1O)、中剂量阿托伐他汀组(阿托伐他汀25 mg·kg-1·d-1,n=10)和高剂量阿托伐他汀组(阿托伐他汀50 mg·kg-1·d-1,n=30).于干预第0、4、8周分别行口服葡萄糖耐量试验(OGTr),测定血糖、血清胰岛素,计算稳态模型评估-β细胞功能指数(HOMA-β)、第一时相胰岛素分泌指数(△I30/△G30)、稳态模型评估-胰岛素抵抗指数(HOMA-IR)、胰岛素曲线下面积(AUCi)、葡萄糖曲线下面积(AUCg)和处置指数.然后将高剂量阿托伐他汀组部分大鼠采用随机数字表法分为两组,继续给药组仍给予高剂量阿托伐他汀灌胃,洗脱组改为生理盐水灌胃,4周后再次行OGTT检测.并取血行甘油三酯、总胆固醇检测.结果 干预8周后高剂量阿托伐他汀组OGTT 0、15、30、60、120 min的胰岛素水平及HOMA-β、△I30/△G30、AUCi、AUCg、HOMA-IR均低于正常对照组(F=4.168 ～ 306.493,P均＜0.05);干预4周时各组及干预8周时中、低剂量阿托伐他汀组均未见相似效应(P均＞0.05).经4周药物洗脱期后,洗脱组的OGTT0、15、30、60、120 min胰岛素水平(F=4.64 ～ 15.58,P均＜0.05)及上述指标均高于继续给药组(t=29.044、4.433、4.429、2.964,P均＜0.05).但各剂量阿托伐他汀组间血糖和处置指数均未见明显影响(P均＞0.05).HOMA-β、△I30/△G30、AUCi随阿托伐他汀剂量的增加和时间的延长,均逐渐降低,具有剂量及时间依赖关系(F=213.970、63.839、18.222,P均＜0.01).HOMA-IR、AUCg随阿托伐他汀剂量的增加逐渐降低,随着时间的延长逐渐升高,也呈剂量及时间依赖关系(F=214.437,P ＜O.01;F=9.33,P ＜O.05).结论 阿托伐他汀可抑制大鼠胰岛β细胞胰岛素分泌,改善胰岛素敏感性,并与给药剂量和时间有关,但对血糖影响不明显.     

阿托伐他汀通过抑制NF-κB对抗大鼠缺血再灌注心肌炎症反应和凋亡的机制

目的:观察阿托伐他汀预处理对大鼠心肌缺血再灌注损伤(MIRI)肿瘤坏死因子(TNF)和白细胞介素-l(IL-1)、心肌细胞内Caspases-3和NF-κB表达的影响,探讨阿托伐他汀的心肌保护作用机制。方法:将40只雄性SD大鼠随机等分为4组:假手术组(A组,0.9%氯化钠溶液5ml/d),缺血再灌注组(B组,0.9%氯化钠溶液5ml/d)、阿托伐他汀标准剂量预处理组(C组,阿托伐他汀20mg/d)和阿托伐他汀强化剂量预处理组(D组,阿托伐他汀40mg/d)。灌胃7d后,第8天制作大鼠在体心肌I/R模型,结扎左冠状动脉前降支30min,再灌注120min后,用ELISA法检测心肌中TNF-α和IL-1β水平,Western blot检测活化Caspase-3和NF-κB的表达。结果:与B组比较,C组TNF-α、IL-1β、Caspases-3、NF-κB水平均明显减少(均P0.05);与C组比较,D组TNF-α、IL-1β、Caspases-3及NF-κB表达减少更为明显(均P0.05)。结论:阿托伐他汀预处理明显抑制炎症反应,减少细胞凋亡,减轻MIRI损伤,呈现较强的心肌保护作用,其机制可能与抑制心肌NF-κB表达有关。     

阿托伐他汀对糖尿病大鼠视网膜核因子-κB表达的影响

目的 探讨他汀类药物对糖尿病大鼠视网膜核因子(NF)-κB表达的影响及其可能机制.方法 雄性SD大鼠60只,随机抽40只腹腔注射链脲佐菌素65 mg/kg建立糖尿病模型,余20只为正常对照组.成模大鼠随机分成两组,糖尿病非药物干预组及阿托伐他汀干预组.干预组予阿托伐他汀(2 mg·kg-1·d-1)灌胃,对照组及糖尿病非药物干预组给予等量饮用水.大鼠分别于3,6个月时按比例处死.取一眼视网膜组织抽提RNA,另一眼固定后做免疫组织化学观察.RT-PCR法扩增NF-κB基因,比较3组大鼠的NF-κB mRNA表达差异.免疫组织化学法观察NF-κB蛋白表达差异.结果 PCR结果示糖尿病大鼠视网膜NF-κB mRNA表达较正常大鼠明显增高(P＜0.05),药物干预的大鼠,NF-κB mRNA表达比糖尿病非药物干预组明显减少(P＜0.05).免疫组织化学结果示视网膜上,NF-κB主要分布在血管层,糖尿病大鼠视网膜中NF-κB阳性的细胞比正常组明显增多(P＜0.05),且着色较深.阿托伐他汀干预组NF-κB阳性的细胞比糖尿病大鼠明显减少(P＜0.05),且着色较浅.结论 阿托伐他汀能降低糖尿病大鼠视网膜中NF-κB mRNA及NF-κB蛋白质的表达,减缓视网膜病变进展.     

阿托伐他汀联合普罗布考对冠心病患者ADMA浓度的影响

目的 探讨阿托伐他汀与普罗布考对非对称二甲基精氨酸(asymmetric dimethyl arginine,ADMA)浓度的影响及可能的作用机制.方法 冠脉粥样斑块患者随机分为阿托伐他汀治疗组(A组,阿托伐他汀20 mg/d口服,睡前服用)、普罗布考治疗组(B组,普罗布考500 mg口服,每日2次)、阿托伐他汀合用低剂量普罗布考治疗组(C组,阿托伐他汀20 mg/d,睡前服用;普罗布考250 mg,每日2次口服)、阿托伐他汀合用高剂量普罗布考治疗组(D组,阿托伐他汀20 mg/d,睡前服用;普罗布考500 mg,每日2次口服),共治疗6个月.采用高效液相色谱方法(HPLC)检测治疗前后ADMA浓度,比色法测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平,血管内超声检测治疗前后冠脉粥样斑块负荷.结果 各组患者治疗后较治疗前ADMA浓度均明显降低(P＜0.05),其中C组与D组较A组与B组降低更为显著(P＜0.05).血脂水平A、C、D组较B组下降更为显著(P＜0.05),C组与D组血脂下降水平差异无显著性,LDL-C水平B、C、D组较A组下降明显(P＜0.05).各组治疗前后粥样斑块负荷无显著差异.结论 ADMA是一个独立的冠心病危险因子,ADMA浓度升高可能是冠状动脉粥样硬化起始和病情进展的标志.     

阿托伐他汀对糖尿病大鼠肾皮质肾上腺髓质素受体表达的影响

目的探讨肾上腺髓质素受体(ADMR)在糖尿病(DM)大鼠肾脏病变时的变化及阿托伐他汀对ADMR表达的影响。方法将SD大鼠分为3组:正常对照组、DM对照组和阿托伐他汀干预组。采用腹腔注射链脲佐菌素(STZ)制备DM动物模型,阿托伐他汀15mg·kg-1·d-1灌胃。通过RT-PCR方法检测肾皮质中ADMR mRNA的表达,运用Western印迹方法检测肾皮质中ADMR蛋白的表达。结果(1)阿托伐他汀干预组大鼠体重、糖化血红蛋白(HbA1C)及血糖与DM组比较差异无统计学意义,24h尿白蛋白排泄率显著降低[(35.9±1.7)μg/24hvs(19.8±1.5)μg/24h,P<0.01];(2)阿托伐他汀干预组大鼠肾皮质中ADMR mRNA及蛋白的表达均显著高于DM组(均P<0.05)。结论阿托伐他汀可上调DM大鼠肾皮质中ADMR基因和蛋白的表达,ADMR可能参与了阿托伐他汀对肾脏的保护作用。     

阿托伐他汀早期干预对急性心肌梗死心肌细胞凋亡的影响

目的探讨不同剂量阿托伐他汀提早干预治疗,对兔急性心肌梗死(AMI)细胞凋亡的影响。方法24只新西兰兔随机分为3组:①对照组:不予药物干预;②低剂量组:0.5mg·kg-1·d-1阿托伐他汀;③高剂量组:5mg·kg-1·d-1阿托伐他汀。在药物干预3d后制作AMI模型,检测心肌梗死及其边缘区细胞凋亡率并观察心肌Bax和Bcl-2表达。结果①高剂量组心肌细胞凋亡率明显低于对照组和低剂量组(P<0.05,P<0.01)。②高剂量组Bcl-2表达高于对照组及低剂量组(P<0.01,P<0.05),对照组与低剂量组差异无统计学意义;三组Bax表达均较高,但组间比较,差异无统计学意义。③Pearson线性相关分析显示梗死及其边缘区心肌细胞凋亡率与相应区域Bcl-2表达呈负相关,与心肌组织Bax表达无明显相关关系。结论高剂量阿托伐他汀降低梗死区及其边缘区心肌细胞凋亡率,与低剂量相比显示出更好保护作用。     

阿托伐他汀对急性心肌梗死大鼠边缘带心肌IL-8表达与室性心律失常的影响

目的:探讨阿托伐他汀对急性心肌梗死后室性心律失常的抑制作用及机制。方法:45只雄性急性心肌梗死大鼠随机均分为高、低剂量阿托伐他汀组及急性心肌梗死组(每组15只)。另取10只大鼠作为假手术组。高、低剂量阿托伐他汀组每日分别给予阿托伐他汀10mg·kg-1·d-1、20mg·kg-1·d-1灌胃1周,假手术组和急性心肌梗死对照组不予治疗。第1周末以程序电刺激诱发各组大鼠室性心律失常后,假手术组取位于左心室游离壁心肌组织,心肌梗死各组取位于左心室梗死边缘带心肌组织检测白细胞介素(IL)-8表达。结果:急性心肌梗死组梗死边缘带IL-8表达水平及室性心律失常诱发率均高于假手术组(P0.01),低剂量阿托伐他汀组梗死边缘带IL-8表达水平及室性心律失常诱发率显著低于急性心肌梗死组(P0.05)。高剂量阿托伐他汀组梗死边缘带IL-8表达水平及室性心律失常诱发率显著低于低剂量组(P0.05)。结论:阿托伐他汀可能通过抑制IL-8过度表达来降低室性心律失常发生率,其作用呈剂量依赖性。     

瑞舒伐他汀与阿托伐他汀对急诊PCI患者血脂及炎症因子的影响

目的 比较国产瑞舒伐他汀与阿托伐他汀对急诊冠脉介入术(PCI)术后患者血脂及炎症因子水平的影响.方法 入选70例急性心肌梗死患者随机分为两组.A组患者PCI术前给予瑞舒伐他汀10 mg,B组患者PCI术前给予阿托伐他汀40 mg,PCI术后两组他汀按原剂量维持.检测两组治疗前后血清C反应蛋白(CRP)、白介素-6(IL-6)及血脂水平.结果 两组治疗后与治疗前相比总胆固醇(TC)、低密度脂蛋白(LDL-C)、CRP、IL-6 、三酰甘油(TG)均明显降低(P<0.05或P<0.01),高密度脂蛋白(HDL-C)无明显变化(P>0.05).结论 国产瑞舒伐他汀10 mg剂量具有与进口阿托伐他汀40 mg剂量类似的调脂抗炎作用,能降低急诊PCI患者血脂及炎症因子水平.     

阿托伐他汀对动脉粥样硬化大鼠血浆溶血磷脂酸的干预作用

目的探讨动脉粥样硬化(AS)大鼠血浆溶血磷脂酸(LPA)的变化及阿托伐他汀的干预作用。方法将33只W istar雄性大鼠随机分为对照组、AS模型组、阿托伐他汀治疗组,每组11只。模型组和治疗组在实验开始时,一次性腹腔注射维生素D360万U/kg,以后喂食高脂饮食;对照组喂食基础饲料。4周后治疗组灌胃给予阿托伐他汀治疗,第8周末处死大鼠,取主动脉观察形态及病理学变化,并检测血脂、血浆LPA及LPA相似磷脂水平。结果AS模型组主动脉出现典型AS斑块,与对照组比较,其血浆LPA水平为(4.7±0.8)μmol/L,显著高于对照组的(2.3±0.6)μmol/L及阿托伐他汀治疗组的(3.5±0.6)μmol/L(均P<0.05)。与模型组比较,阿托伐他汀治疗组的血脂水平均明显改善(P<0.05),主动脉AS程度也较轻。结论LPA参与了AS的形成过程,而阿托伐他汀可以降低AS大鼠血浆LPA水平,对AS的发生发展有明显的抑制作用。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.