一氧化氮与卵巢生理

NO是一种结构简单的气体,是脊椎动物体内已发现的分子量最小的生物活性分子。NO作为一种信使分子,生物作用广泛,在生殖系统发挥重要作用。本文着重介绍NO作为卵巢内重要的调节因子,在调节卵泡发育、卵母细胞成熟、排卵、黄体的形成与退化、激素合成等方面的研究进展。     

高血压病血管内皮功能障碍及治疗

内皮细胞功能障碍是近年来的热门研究课题,从基础到临床受到广泛重视。高血压是发病率最高的心血管疾病,其发病环节与内皮细胞功能关系密切,二者均是心脑血管事件链中的重要环节。本文回顾了多种内皮因子的功能及其与高血压的关系,高血压病内皮功能障碍的可能机制,肱动脉超声检查方法以及内皮功能障碍的治疗对策。     

大鼠上丘一氧化氮合酶阳性神经元的发育

目的：研究大鼠胚胎时期及生后早期一氧化氮合酶(NOS)阳性神经元在上丘的分布，进一步探讨一氧化氮(NO)在上丘发育过程中的作用。方法：应用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶(NADPH—d)组织化学方法观察孕17d起至生后14d大鼠上丘NOS阳性神经元的发育。结果：孕20d上丘深白层与深灰层出现NOS阳性神经元。P0上丘中层也观察到NOS阳性神经元。随着发育，阳性神经元增多，胞体增大，染色加深。到P14，视神经层出现少许：NOS阳性神经元，浅灰层观察到大量的NOS阳性神经元。结论：胚胎20天上丘深层首先出现NOS阳性神经元并沿腹背方向发生，提示NO在上丘发育过程中起着重要作用。     

Effect of curcumin on nitric oxide synthase expression in Iipopolysaccharide-activated microglia cells and the anti-oxidative effect of curcumin

BACKGROUND: It has been demonstrated that curcumin can increase the activities of various anti-oxidase in blood and tissue, effectively eliminate various free radicals, reduce the production of peroxisome, and alleviate oxidative stress reaction. Whether it has the same effect on microglia? OBJECTIVE: To observe the effects of curcumin on the expressions of inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB), and superoxide dismutase (SOD) in microglial cell line BV stimulated by lipopolysaccharide (LPS). DESIGN: An observational comparative study. SETTING: Research Room of Biochemistry, Medical College of Nantong University. MATERIALS: Mice microglia cell line BV, iNOS and NF-κB reporter gene plasmids were presented by Dr. Bhat.NR. from the Medical University of South Carolina (USA). Curcumin was produced by the Xi'an Branch of China Chengdu Scholar Bio-Tech. Co.,Ltd.; LPS (E.Coli O26:B6), anti-mice iNOS monoclonal antibody, horseradish peroxidase labeled goat-anti-mice IgG were the products of Sigma Company (USA). METHODS: The experiments were carried out in the Research Room of Biochemistry, Medical College of Nantong University from May 2006 to April 2007. ① Detection of iNOS: The cells were seeded onto 24-well plate at the density of 1×105, After the cells had adhered to the cover glasses, the cells were grouped as negative control group (the primary antibody was replaced by phosphate buffered solution PBS); normal control group (the cells were normally cultured); LPS-treated group (the cells were treated with LPS for 24 hours); curcumin+LPS group (the cells were treated with curcumin for 1 hour and LPS for 24 hours). The expressions of iNOS protein were detected with immunocytochemical staining. ② Determination of iNOS and NF-κB gene activities: According to the introduction of the kit for transfection, iNOS or NF-κB report gene plasmids were transiently transfected with LipofectamineTM2000 liposomes into the cells in the 24-well plate for 24 hours. The cells were divided into normal control group (the cells were normally cultured after transfected with report gene plasmids); blank plasmid group (the cells were normally cultured after transfected with blank plasmids); LPS-treated group (the cells were treated with LPS for 4 hours after transfected with report gene plasmids); curcumin+LPS group (the cells were treated with curcumin for 1 hour and LPS for 24 hours after transfected with report gene plasmids). The content of luciferase in the cell lysis buffer was determined after cell lysis. ③ Determination of SOD activity: The cells were seeded into culture bottle at the density of 1×106, and the divided into four groups, including normal control group (the cells were normally cultured); LPS-treated group (the cells were treated with LPS for 24 hours); curcumin+LPS group (the cells were treated with curcumin for 1 hour and LPS for 24 hours); vitamin C+LPS group (the cells were treated with vitamin C for 1 hour and LPS for 24 hours). The SOD activity was determined with xanthine oxidase and quantitative colorimetric assay. MAIN OUTCOME MEASURES: The expressions of iNOS protein, iNOS and NF-κB, and the activity of SOD were observed. RESULTS: ① Expression of iNOS protein in microglia: The expression of iNOS protein in the LPS-treated group was obviously higher than that in the negative control group (P < 0.01); Those in the curcumin+LPS group were significantly decreased as compared with that in the LPS-treated group (P < 0.01). ② Expressions of iNOS and NF-κB genes: The expressions of iNOS and NF-κB genes in the LPS-treated group were significantly higher than those in the normal control group (P < 0.01); Those in the curcumin+LPS group were significantly lower than those in the LPS-treated group (P < 0.01). ③ SOD activity: The activity of SOD in the LPS-treated group was significantly lower than those in the normal control group (P < 0.01). It in the curcumin+LPS group and vitamin C +LPS group was significantly higher than that in the LPS-treated group (P < 0.01). CONCLUSION: Curcumin could inhibit the expression of iNOS in the activated microglia, and it also has the abilities in eliminating free radicals and antagonizing lipid peroxidation.     

以胆酸为载体的肝靶向疗法

通过肝靶向给药技术将化学治疗药物选择性地投放于肝脏,能够减轻或避免其全身的毒副作用.胆酸是唯一的口服有效的小分子肝靶向载体,以胆酸为载体的肝靶向疗法为肝病及肝脏代谢性疾病提供了新的疗法.如胆酸-一氧化氮供体靶向偶合物能够选择性地将一氧化氮投放于肝脏,产生治疗肝硬化的作用;胆酸-脂肪酸靶向偶合物能够选择性地调节肝脏的脂代谢,具有治疗胆结石、脂肪肝和动脉粥样硬化的作用;胆酸-米非司酮偶合物能够选择性地作用于肝脏,产生特异性的降糖作用,而没有全身副作用.     

Effects of chronic treatment with a nitric oxide donor on nerve conduction abnormalities and endoneurial blood flow in streptozotocin-diabetic rats

Abstract. This study examined the ability of nitrova-sodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity ( P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively ( P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% ( P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow ( P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively ( P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action.     

液膜法提取硝酸水溶液中Ag~+的工艺过程

液膜的组成为:2%石油硫醚-4%多丁二酰亚胺-94%煤油,内相试剂为:1～2mol/L的氨水溶液。较为适宜的操作条件为:乳水比为1:3;内油比为0.8:1;外相硝酸浓度为0.5～1mol/L;常温操作。当料液中的银离子浓度小于800ppm时,一次提取率可达97%以上。本工艺具有分离速度快,效率高、选择性好等优点。     

Induction of NADPH-diaphorase activity in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance

Preconditioning of the brain with sublethal ischemia induces tolerance to subsequent lethal periods of ischemia (ischemic tolerance). In this study, we used NADPH-diaphorase histochemistry to investigate the postischemic changes of nitric oxide synthase (NOS) in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance. Forebrain ischemia was induced by 4-vessel occlusion for 3 min as an ischemic preconditioning. Three days after the preconditioning or sham operation, second ischemia was induced for 6 min. A transient increase in NADPH-diaphorase activity, beginning after 2 h and maximal after 1 day, was observed in CA1 pyramidal neurons of rats subjected to 3 min of preconditioning ischemia as well as 6 min of subsequent ischemia both with and without preconditioning. In addition, expression of NADPH-diaphorase activity was seen in reactive glial cells in the damaged CA1 region of animals subjected to 6 min of ischemia without preconditioning. Thus, direct involvement of increased NADPH-diaphorase activity in ischemic tolerance was not suggested because the increased NADPH-diaphorase activity preceded the induction of ischemic tolerance which takes place 1–7 days after preconditioning. However, the present findings suggest that the induction of neuronal NADPH-diaphorase activity occurs in response to cerebral ischemia.     

Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats

The effects of intraperitoneal and methyl ester, specific inhibitors of nitric oxide (NO) synthase, were examined on the pentylenetetrazol (PTZ)-induced seizures in rats. The incidence and latency for the onset of myoclonic jerks, clonic seizures, and tonic generalized extension were observed as specific parameters among PTZ-induced seizures. Both drugs preferentially suppressed the tonic generalized extension and prolonged the latency for the onset of each parameter, suggesting NO has a significant effect on the PTZ-induced seizure.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.