兔不全梗阻性膀胱一氧化氮合酶神经和内皮素-1含量的改变及意义

目的　研究一氧化氮合酶 (NOS)神经、内皮素 (ET) - 1在兔不全梗阻性膀胱中的改变和意义。方法　运用 NADPH组织化学及放射免疫分析技术对 1 0只成年雄性新西兰白兔不全梗阻性膀胱及 1 0只同龄雄性新西兰白兔无梗阻性膀胱的兔血浆、尿液及膀胱平滑肌组织中 ET- 1和膀胱平滑肌中 NOS神经进行研究。结果　实验组兔膀胱体、膀胱颈部粘膜及膀胱体平滑肌 NOS神经均明显减少 (膀胱体粘膜为 P<0 .0 5,膀胱颈粘膜为 P<0 .0 1 ,膀胱体平滑肌为 P<0 .0 5) ;实验组较对照组血浆与尿液中 ET- 1含量均明显增高 (血浆 3 w组与血浆 6 w组均为 P<0 .0 5;尿液 3 w组与 6 w组均为 P<0 .0 0 1 ) ;实验组较对照组膀胱体部平滑肌组织 ET- 1含量明显升高 (P<0 .0 5)。结论　 NOS神经的减少和 ET- 1的上调对兔不全梗阻性膀胱的功能和结构变化具有一定作用 ,为梗阻性膀胱的病理生理变化提供了一个较为合理的解释。血浆、尿液中 ET- 1在兔不全梗阻性膀胱中的含量上调 ,并可作为膀胱出口梗阻诊断的重要参数。     

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐?β, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐?β, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.     

NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis

Background and purposePulmonary fibrosis (PF) is a progressing lung injury initiated by pulmonary inflammation (PI). Bleomycin (BLM) is the most common pathogenesis of PF through early PI and extensive extracellular matrix deposition. This study is aimed to determine whether NO-releasing KMUP-1 inhibits PI and PF, and if so, the benefits of KMUP-1S resulted from simvastatin (SIM)-bonding to KMUP-1.Experiment approachC57BL/6 male mice were intra-tracheally administered BLM (4 U/kg) at day 0. KMUP-1 (1–5 mg/kg), KMUP-1S (2.5 mg/kg), SIM (5 mg/kg), Plus (KMUP-1 2.5 mg/kg + SIM 2.5 mg/kg), and clarithromycin (CAM, 10 mg/kg) were orally and daily administered for 7 and 28 days, respectively, to mice, sacrificed at day-7 and day-28 to isolate the lung tissues, for examining the inflammatory and fibrotic signaling and measuring the cell population and MMP-2/MMP-9 activity in broncholaveolar lavage fluid (BAL).Key resultsKMUP-1 and KUP-1S significantly decreased neutrophil counts in BAL fluid. Fibroblastic foci were histologically assessed by H&E and Masson's trichrome stain and treated with KMUP-1 and references. Lung tissues were determined the contents of collagen and the expressions of TGF-β, α-SMA, HMGB1, CTGF, eNOS, p-eNOS, RhoA, Smad3, p-Smad3, MMP-2 and MMP-9 by Western blotting analyses, respectively. These changes areregulated by NO/cGMP and inhibited by various treatments. KMUP-1 and KMUP-1S predominantly prevented HMGB1/MMP-2 expression at day-7 and reduced TGF-β/phosphorylated Smad3 and CTGF at day-28.Conclusions and implicationsKMUP-1 and KMUP-S restore eNOS, inhibit iNOS/ROCKII/MMP-2/MMP-9, attenuate histologic collagen disposition and reduce BALF inflammatory cells, potentially useful for the treatment of BLM-lung PF.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

基因治疗原发性高血压的新途径:内皮型一氧化氮合成酶CDNA腺病毒载体在人胎肾293细胞的表达

研究内皮型一氧化氮合成酶（endothelialnitric oxide synthase,eNOS)CDNA 腺病毒载体 PadRSVeNOSCDNA 导入在人胎肾 293细胞 ( )中的表达。方法:大量制备及纯化质粒 eNOSCDNA ,将纯化eNOSCDNA 载体通过脂质体转染 293细胞48h 后,应用化学比色法测定293细胞提取物NOS 活性。结果:被转染 293细胞 NOS活性显著提高于未转染293细胞 NOS 活性犤( 0.62±0.03),(0.093±0.01)kU /L,P <0.001犦。结论:PA dRSVeNOSCDNA 导入人胎肾 293细胞是一种能使 NOS 活性显著升高的方法,为基因治疗原发性高血压及肾脏血管性疾病研究提供一条新的途径。     

胃癌中一氧化氮合酶表达与幽门螺旋杆菌以及胃癌血管生成之间的关系

目的研究诱导型一氧化氮合酶（iNOS）和内皮型一氧化氮合酶（eNOS）在人胃癌中的表达;探讨两者与人胃癌血管生成和临床病理特征的关系;研究幽门螺旋杆菌（H.pylori）在肿瘤发生机制中对NO的影响。方法应用免疫组织化学方法检测59例胃癌及癌旁组织iNOS和eNOS的表达,快速尿素酶及组织学检测幽门螺旋杆菌。第VⅢ因子相关抗原（F-VⅢRAg）血管内皮细胞特异性染色计数肿瘤微血管密度（MVD）。结果①胃癌组织中iNOS阳性率明显高于癌旁组织,二者之间差异有显著性（P〈0.05）,eNOS的阳性率略高于癌旁组织,二者之间差异无显著性（P〉0.05）。②iNOS、eNOS表达与胃癌分化程度无明显相关。③iNOS表达与胃癌的浸润程度及淋巴结转移呈正相关,eNOS表达与胃癌的浸润程度及淋巴结转移无关。④H.pylori感染与iNOS呈正相关,与eNOS无关。⑤iNOS的表达与胃癌MVD呈正相关,eNOS的表达与胃癌MVD无相关性。结论①iNOS在胃癌的发生发展中起重要作用。②H.pylori在致癌机制中可有iNOS的参与。③iNOS对胃癌血管的生成具有促进作用。     

Inhibitory Effects of Ginsenoside-Rb2 on Nicotinic Stimulation-Evoked Catecholamine Secretion

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 µM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 µM) also time-dependently inhibited the CA secretion evoked by DMPP (100 µM, a selective neuronal nicotinic receptor agonist) and high K⁺ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 µg/mL), the secretory responses of CA evoked by veratridine (a selective Na⁺ channel activator (50 µM), Bay-K-8644 (an L-type dihydropyridine Ca²⁺ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca²⁺-ATPase inhibitor, 10 µM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 µM) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 µM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca²⁺ and Na⁺ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca²⁺ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.     

Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session).