钙离子在心肌缺血预适应中的作用

目的 观察钙离子变化对心肌缺血预适应内源性保护机制的影响。方法将50只雄性SD大鼠随机分为五组，缺血对照（IC）组；缺血预适应（IP）组；缺血预适应＋维拉帕米（IP＋Vera）组；钙通道激动剂（Bay8644）组；L-型钙通道阻滞剂（维拉帕米，Verapamil）组。实验中观察缺血前及再灌后左心功能，检测乳酸脱氢酶（LDH）、三磷酸腺苷（ATP）等含量并辅以心肌超微结构观测。结果与IC组相比，IP组、Bay8644组各项指标均提示心功能恢复好转（P〈0．05），且IP组与Bay8644组相比较，各项指标差异无统计学意义（P〉0．05）；在IP组中加入维拉帕米后，各项指标均提示心肌损伤明显加重（P〈0．05）。结论（1）心肌缺血预适应可诱导出心肌内源性保护作用。（2）钙通道拮抗剂可通过减少钙离子内流而阻断心肌缺血预适应的心肌保护作用。（3）增加钙离子内流可模拟IP的心肌保护作用。     

热休克蛋白70的肺保护作用研究

热休克蛋白(HSP)是生物细胞受到伤害性刺激时,由HSP基因编码合成的一类生物进化上最保守的蛋白,具有抗炎、抗氧化、抑制凋亡以及分子伴侣作用,HSP对各种刺激还具有迅速的反应能力,在许多细胞活动中扮演着重要的角色。而其中最受关注的是HSP70,尽管其在生理状态下,表达量较少,但可通过热预处理、基因转染以及药物等方法诱导其产生,从而发挥脏器保护作用。文章综述其在急性肺损伤中的作用以及相关机制的机制研究进展。     

新生鼠肠道缺乏适应性细胞保护

目的 探讨新生大鼠肠道是否存在适应性细胞保护作用。方法 新生大鼠称重后随机分到各组，分别予生理盐水（NS）、生理盐水＋盐酸（NS＋HCl）、盐酸（HCl）、醋酸，（AA，）灌肠作预处理，30min后再给予醋酸（AA）灌肠（另设一组用NS作预处理，30min后再予NS灌肠）；24h后称重，然后断颈处死；取出近端结肠用以组织病理学评分，并留取血清标本做髓过氧化物酶（MPO）活性检测和白细胞介素6（IL-6）浓度检测。结果 （NS＋HCl）＋AA、HCl＋AA、AA，＋AA各组与NS＋AA组比较，组织病理学评分、髓过氧化物酶活性、血清白细胞介素6（IL-6）浓度各方面反而增加，P〉0．05；试验前后24h体重增长反而较少，P〉0．05。（NS＋HCl）＋AA、HCl＋AA、AA，＋AA各组与NS＋NS组比较，组织病理学评分、髓过氧化物酶活性、血清白细胞介素6（IL-15）浓度各方面明显增加，P〈0．05；试验前后24h体重增长明显减少，P〈0．05。结论 新生鼠的肠道缺乏适应性细胞保护作用。     

Using behaviour to predict stroke severity in conscious rats: post-stroke treatment with 3', 4'-dihydroxyflavonol improves recovery

Prognostic models are used to predict outcome in stroke patients and to stratify treatment groups in clinical trials. No one has previously attempted to use such models in stroke recovery studies in animals. We have now shown the predictive value of assigning stroke severity ratings, based on behaviours displayed in conscious rats during infusion of endothelin-1 to constrict the middle cerebral artery, on neurological and histological outcomes. The validity of prior stratification of treatment groups according to stroke ratings was tested by assessment of the protective potential of synthetic flavonol, 3',4'-dihydroxyflavonol (DiOHF). Neurological deficits and performance on the sticky label test were evaluated before and at 24, 48 and 72 h post-stroke. Histopathology was assessed at 72 h. Positive correlations between stroke ratings and neurological deficit scores were found at 24 (r=0.58, P<0.001), 48 (r=0.53, P<0.001) and 72 (r=0.56, P<0.001) h post-stroke, with more severe strokes associated with worse deficit scores. Similar correlations were observed with the sticky label test. Higher stroke ratings also correlated with greater infarct volumes (total infarct volume: r=0.74, P<0.0001). Treatment with DiOHF (10 mg/kg i.v. given 3, 24 and 48 h post-stroke) significantly reduced infarct volume and restored neurological function in rats with modest stroke ratings (P<0.01), but not in rats with high stroke ratings. These results suggest that stroke ratings, based on behavioural assessment as the stroke develops, reliably predict histopathological and functional outcomes and allow stratification of treatment groups. DiOHF given after stroke improves outcomes in moderate strokes, and therefore has cytoprotective potential.     

血管内皮生长因子基因转移对6-羟多巴胺诱导的多巴胺能细胞损伤的保护作用

目的探讨血管内皮生长因子(VEGF)基因转移对6-羟多巴胺(6-OHDA)诱导的多巴胺能细胞损伤的保护作用。方法用腺病毒载体携带VEGF165基因(Ad-VEGF165)感染PC12细胞,并设腺病毒携带的β-半乳糖苷酶基因(Ad-LacZ)感染组和磷酸盐缓冲液(PBS)处理组作对照,基因转移成功后,用6-OHDA处理细胞,另设正常对照(不加6-OHDA)。四甲基偶氮唑盐法(MTT)测定细胞活性,免疫荧光细胞化学法检测细胞酪氨酸羟化酶(TH)表达,高效液相色谱检测细胞分泌功能。结果Ad-VEGF165感染组细胞吸光度A_(570)(0.31±0.07),高于Ad-LacZ感染组(0.15±0.07)和PBS处理组(0.13±0.05),但低于正常对照组(0.55±0.10),分别与各组比较,差异均有统计学意义(均为P<0.01);免疫荧光染色显示Ad-VEGF组细胞胞浆平均荧光强度(86.75±21.62)高于Ad-LacZ组(51.53±1 7.49)及PBS组(54.19±15.82),但低于正常对照组(110.39±24.21),分别与各组比较,差异均有统计学意义(均为(P<0.05);Ad-VEGF感染组细胞培养液中多巴胺和去甲肾上腺素含量也高于Ad-LacZ感染组和PBS处理组。结论腺病毒介导的VEGF基因转移对6-OHDA诱导的多巴胺能细胞损伤具有保护作用。     

A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers

AIM: To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection (ESD) gastric ulcers.METHODS: Patients with gastric tumors indicated for ESD were prospectively studied. After ESD, all patients were treated with intravenous omeprazole for the first 3 d. Patients were then randomly assigned to oral lafutidine or rabeprazole. Ulcer size, ulcer size reduction rate, and ulcer stage were evaluated 4 wk later. Occurrence of complication was monitored throughout the 4-wk period.RESULTS: Sixty five patients were enrolled in the study, and 60 patients were subjected to the final analysis. In the lafutidine group (30 lesions in 29 patients), initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm, respectively. In the rabeprazole group (34 lesions in 31 patients), the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm, respectively. Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%, respectively (P = 0.974). Ulcer stage 4 wk post-ESD did not differ significantly between the two groups (P = 0.868). Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period, although the difference of bleeding rate between the two groups was not statistically significant (P = 0.157).CONCLUSION: Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.     

曲美他嗪治疗急性心肌梗死的临床研究

目的评价在急性心肌梗死（AMI）再灌注治疗前开始应用曲美他嗪（TMZ）对再灌注治疗的影响。方法60例接受再灌注治疗的AMI患者随机分为TMZ组和对照组。经冠状动脉造影证实血管再通。TMZ组患者在确诊AMI后即刻服用TMZ60mg,随后给予20mg,3次／d。比较两组患者再灌注治疗前后的心电图ST段降幅以及血浆丙二醛（MDA）、内皮素（ET-1）水平的变化。记录住院期间和发病3个月内的主要临床事件。结果TMZ组患者再灌注治疗后ST段下降幅值显著高于对照组[（7．14±3．50）mm比（3．79±1．32）mm,P=0．041];ST段下降幅度〉70％者显著多于对照组（68．8％比42．9％,P=0．043）。TMZ组的血MDA水平于再灌注4h后各个时间段内均显著低于对照组。TMZ组的血ET-1水平于再灌注后8h和第7天显著低于对照组。结论AMI患者于再灌注治疗前即开始应用TMZ可增加ST段降低的幅值,减少MDA的生成及ET-1的释放,具有心肌细胞保护作用。     

Attenuation of cadmium chloride induced cytotoxicity in murine hepatocytes by a protein isolated from the leaves of the herb <Emphasis Type="Italic">Cajanus indicus</Emphasis> L.

Cadmium has been recognized as a strong environmental pollutant. Exposure to this heavy metal occurs through the intake of foodstuffs, drinking water and also via the inhalation of air. Present study was conducted to evaluate the protective effect of a 43 kDa protein, isolated from the leaves of the herb Cajanus indicus, against cadmium-induced cytotoxicity in hepatocytes. For this study, cadmium chloride (CdCl₂) has been used as the source of cadmium. Treatment of hepatocytes with 800 μM CdCl₂ for 3 h caused significant reduction in cell viability in association with the increased levels of glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) leakage. The activities of the antioxidant enzymes, superoxide dismutase, catalase (CAT), glutathione-S-transferase and glutathione reductase, and the levels of cellular metabolites, reduced glutathione (GSH) as well as total thiols have also been decreased under the same treatment. In addition, the toxin enhanced the levels of the lipid peroxidation end products and oxidized glutathione (GSSG). Incubation of hepatocytes with the protein at a dose of 0.1 mg/ml for 3 h prior to the toxin treatment (at a dose of 800 μM for 3 h) restored the activities of all the antioxidant enzymes, the levels of GSH, total thiols, cell viability and also attenuated the increased levels of GPT, ALP, lipid peroxidation and GSSG. In addition, the protein resisted CdCl₂ induced alterations of all the parameters when applied in combination with CdCl₂. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin against CdCl₂ induced cytotoxicity have also been included in the study. Combining all, we would like to say that the protein possessed protective activity against CdCl₂ induced cytotoxicity in mouse hepatocytes probably via its antioxidant property. Mahua Sinha and Prasenjit Manna contributed equally in the study.     

The multifunctional human ocular melanocortin system

Immune privilege in the eye involves physical barriers, immune regulation and secreted proteins that together limit the damaging effects of intraocular immune responses and inflammation. The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) normally circulates in the aqueous humour of the anterior chamber and the vitreous fluid, secreted by iris and ciliary epithelium, and retinal pigment epithelium (RPE). α-MSH plays an important role in maintaining ocular immune privilege by helping the development of suppressor immune cells and by activating regulatory T-cells. α-MSH functions by binding to and activating melanocortin receptors (MC1R to MC5R) and receptor accessory proteins (MRAPs) that work in concert with antagonists, otherwise known as the melanocortin system. As well as controlling immune responses and inflammation, a broad range of biological functions is increasingly recognised to be orchestrated by the melanocortin system within ocular tissues. This includes maintaining corneal transparency and immune privilege by limiting corneal (lymph)angiogenesis, sustaining corneal epithelial integrity, protecting corneal endothelium and potentially enhancing corneal graft survival, regulating aqueous tear secretion with implications for dry eye disease, facilitating retinal homeostasis via maintaining blood-retinal barriers, providing neuroprotection in the retina, and controlling abnormal new vessel growth in the choroid and retina. The role of melanocortin signalling in uveal melanocyte melanogenesis however remains unclear compared to its established role in skin melanogenesis. The early application of a melanocortin agonist to downregulate systemic inflammation used adrenocorticotropic hormone (ACTH)-based repository cortisone injection (RCI), but adverse side effects including hypertension, edema, and weight gain, related to increased adrenal gland corticosteroid production, impacted clinical uptake. Compared to ACTH, melanocortin peptides that target MC1R, MC3R, MC4R and/or MC5R, but not adrenal gland MC2R, induce minimal corticosteroid production with fewer adverse systemic effects. Pharmacological advances in synthesising MCR-specific targeted peptides provide further opportunities for treating ocular (and systemic) inflammatory diseases. Following from these observations and a renewed clinical and pharmacological interest in the diverse biological roles of the melanocortin system, this review highlights the physiological and disease-related involvement of this system within human eye tissues. We also review the emerging benefits and versatility of melanocortin receptor targeted peptides as non-steroidal alternatives for inflammatory eye diseases such as non-infectious uveitis and dry eye disease, and translational applications in promoting ocular homeostasis, for example, in corneal transplantation and diabetic retinopathy.