内源性硫化氢对吸烟大鼠小气道纤维化的保护作用

目的探讨内源性硫化氢（Hzs）对于吸烟诱导的COPD大鼠模型中小气道纤维化的影响。方法32只健康雄性SD大鼠随机分为正常组、吸烟组、吸烟＋Hzs组和吸烟＋炔丙基甘氨酸（PPG）组,采用被动烟雾吸入法,共吸烟4个月,从第3个月起,每日吸烟前给予大鼠腹腔注射生理盐水、硫氢化钠（NaHS）（14μmol／kg）或PPG（37．5mg／kg）,取肺组织切片进行HE染色和天狼星红染色,观察肺组织病理形态改变,对小气道胶原沉积采用半定量分析,并进行小气道病理评分。Westernblot检测肺组织胱硫醚-γ-裂解酶（CGL）、I型胶原蛋白表达水平。结果与正常组比较,吸烟组小气道病理评分明显升高（P〈0．01）,NaHS干预后较吸烟组评分降低（P〈0．05）。偏振光显微镜下观察天狼星红染色切片,吸烟组和吸烟＋PPG组较正常组小气道周围胶原沉积显著增多（P〈0．01）,吸烟＋H2S组较吸烟组明显减少（P〈0．05）。与正常组相比,吸烟组大鼠肺组织I型胶原蛋白含量明显增多（P〈0．05）,NariS干预后I型胶原蛋白含量较单纯吸烟组明显降低（P〈0．05）。结论内源性H2S参与吸烟诱导的COPD大鼠小气道纤维化的病理生理过程,外源性给予H2S对小气道纤维化具有保护作用。     

硫化氢与血管内皮细胞的功能

血管内皮细胞参与血管内多种生理活动,内皮功能障碍将导致各种心血管疾病的发生.近几年来,研究发现新型气体信号分子硫化氢具有抗动脉粥样硬化等心血管疾病的效应:硫化氢促进内皮细胞增殖迁移诱导血管新生;抑制黏附分子分泌;通过打开平滑肌上ATP依赖性K+通道调节血管紧张度;抵抗氧化应激对内皮细胞的损伤等.随着其保护机制的不断发现与证实,硫化氢将有望逐渐应用于临床治疗,其.对内皮的保护作用仍需要做进一步的研究.     

Combined effects of hydrogen sulfide and lipopolysaccharide on osteoclast differentiation in rats

Background: Lipopolysaccharide (LPS) stimulates osteoclast differentiation through toll‐like receptors (TLRs) 2 and 4, and hydrogen sulfide (H₂S) induces osteoclast differentiation. If H₂S activates TLRs, H₂S may enhance the effects of LPS on osteoclast differentiation. The purpose of the present study is to examine the combined effects of sodium hydrogen sulfide (NaHS, an H₂S donor drug) and LPS on osteoclast differentiation and TLR expression in rat periodontal tissue. Methods: Twenty‐eight male Wistar rats (8 weeks old) were divided into four groups (n = 7 per group): a control (no treatment) group and three experimental groups (NaHS group, LPS group, and a combination [NaHS + LPS] group). At 1 day after topical application of NaHS and/or Porphyromonas gingivalis LPS into the gingival sulcus of first molars, the number of tartrate‐resistant acid phosphate (TRAP)‐positive osteoclasts in the periodontal tissue was counted. Expression of TLR2 and TLR4 mRNAs and proteins in the gingival was also assessed. Results: The number of TRAP‐positive osteoclasts was significantly higher in the combination group than in any other group (P <0.01). The combination group had 11.0‐fold higher TLR4 mRNA levels than the control group. TLR4 protein levels were also higher in the combination group than in the NaHS or LPS group. However, the TLR2 mRNA and protein levels were not significantly different in the combination group and the LPS group. Conclusion: In rat periodontal tissue, NaHS and LPS had an additive effect on osteoclast differentiation through activation of the TLR4 pathway but not the TLR2 pathway.     

手足口病患儿血清硫化氢及白细胞介素-6水平改变的研究

目的：研究手足口病(hand,foot and mouth disease,HFMD)患儿血清硫化氢(hydrogen sulfide,H2 S)与白细胞介素(interleukin,IL)-6水平改变的意义。方法选择在我院住院治疗的92例HFMD 患儿为研究对象,根据病情,选择其中48例为重症 HFMD 组,44例为普通 HFMD 组,选择同期健康儿童46例为健康对照组。分别检测其血清 H2 S 及 IL-6水平。结果急性期：重症 HFMD 组与普通 HFMD 组血清 H2 S [(21.72±7.52)μmol /L、(31.86±8.41)μmol /L]水平均明显降低,IL-6[(131.33±17.82)ng /L、(95.48±15.07)ng /L]水平明显升高,与健康对照组[H2 S (55.76±7.80)μmol /L,IL-6(61.31±13.43)ng /L]比较差异有统计学意义(P ﹤0.01);重症 HFMD 组与普通HFMD 组比较差异有统计学意义(P ﹤0.01)。恢复期：重症 HFMD 组血清 H2 S[(34.54±13.21)μmol /L]水平仍低于健康对照组,IL-6[(92.73±15.25)ng /L]水平仍高于健康对照组,差异有统计学意义(P ﹤0.01)。相关性分析显示：重症 HFMD 组与普通 HFMD 组血清 H2 S 与 IL-6水平之间均呈显著负相关(r ＝-0.31,P ﹤0.01;r ＝-0.45,P ﹤0.01)。结论 HFMD 患儿血清 H2 S 和 IL-6水平发生了改变,并且可作为重症 HFMD 患儿早期诊断的指标之一。     

硫化氢供体型美金刚衍生物的合成及其活性

H₂S具有保护缺血再灌注损伤的神经元、显著降低脑梗死面积的作用,但高浓度H₂S产生神经毒性。N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚可以降低高浓度H₂S引起的神经毒性。将硫化氢缓释供体5-对羟基苯基-1,2-二硫杂环戊烯-3-硫酮(ADT-OH)与美金刚通过烷烃连接臂拼合,设计了9个结构全新的化合物I₁~I₉,以ADT-OH为原料,经过4步反应得到目标化合物,其化学结构经¹H NMR、¹³C NMR和HRMS确证。利用MTT法评价不同浓度目标化合物对谷氨酸损伤的HT-22细胞的影响,结果发现,该类化合物在1 μmol/L时能明显提高受损HT-22细胞的生存率(P<0.01),对于谷氨酸诱导损伤的神经元细胞具有较好的保护作用。     

Diallyl sulfide alleviates cisplatin‐induced nephrotoxicity in rats via suppressing NF‐κB downstream inflammatory proteins and p53/Puma signalling pathway

Despite being a potent anticancer drug, nephrotoxicity is an adverse effect which renders the clinical use of cisplatin (Cis) limited. The protective role of diallyl sulfide (DAS); a naturally occurring organo‐sulfide, present in garlic, in cisplatin‐induced nephrotoxicity has been reported earlier. However, the mechanism through which DAS exerts its nephroprotective activity remains elusive. The aim of the current study was to elucidate the possible mechanisms underlying the reno‐protective effect of DAS in cisplatin‐induced nephrotoxicity in rats. DAS was given at 2 dose levels; 50 and 100 mg/kg, orally for 4 consecutive days, starting 1 hour after administration of single dose of cisplatin (3.5 mg/kg, intraperitoneally [i.p.]). The Cis‐induced elevation in serum urea and creatinine, degree of histopathological alterations was significantly ameliorated in cisplatin groups co‐treated with DAS. In addition, DAS significantly restored Cis‐depleted glutathione (GSH) content and superoxide dismutase (SOD) activity and attenuated Cis‐elevated Malondialdehyde (MDA) level. Also, DAS significantly reduced Cis‐increased renal expression of nuclear factor kappa B (NF‐κB) and subsequent pro‐inflammatory mediators; tumour necrosis factor alpha (TNF‐α), interleukin‐1β (IL‐1β), intercellular adhesion molecule‐1 (ICAM‐1) and inducible nitric oxide synthase (iNOS) in kidney tissues. Moreover, co‐treatment with DAS significantly inhibited Cis‐increased caspase‐8 and ‐9 levels. Additionally, DAS significantly mitigated Cis‐induced protein expression of p53, Puma, and Bax while, it significantly restored Cis‐reduced protein expression of Bcl‐xL compared to the Cis group. In conclusion, these results demonstrate that DAS ameliorates cisplatin‐induced nephrotoxicity in rats through enhancement of antioxidant defense, reduction of inflammatory cytokine tissue levels as well as inhibition of apoptosis via p53/Puma signalling pathway.     

纳米硫化镉呼吸道亚慢性暴露对雄性大鼠的生殖毒性

目的探讨纳米硫化镉(CdS)对大鼠睾丸的氧化损伤及对精子的影响。方法 32只雄性清洁级SD大鼠随机分为对照组(蒸馏水)、10 mg/kg、20 mg/kg和30 mg/kg的纳米CdS组,每组8只。采用肺灌注方法染毒,2次/周,持续染毒12周。计算睾丸脏器系数,测定睾丸组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量,观察精子数量、畸形率、活动度和睾丸的病理学变化。结果与对照组相比,30 mg/kg染毒组精子数量、精子活动度降低,10、20、30 mg/kg染毒组精子畸形率增高(P<0.05)。与对照组相比,30 mg/kg染毒组的大鼠睾丸SOD、GSH-Px活力降低(P<0.05),10、20、30 mg/kg染毒组的大鼠睾丸MDA含量增高(P<0.05)。染毒组生精小管内生精细胞脱落,层次减少,各级生精细胞排列紊乱,管内生精细胞疏松、排列紊乱、上皮变薄,管腔内可见脱落的精子细胞。结论纳米硫化镉经呼吸道染毒可致大鼠睾丸病理改变,氧化损伤,并且引起精子数量减少,活动度降低,畸形率增加。     

微波消解-ICP-OES法检测湘产朱砂中重金属的含量

目的建立微波消解-电感耦合等离子体原子发射光谱法（ICP-OES）检测湘产朱砂中Cd、Cr、Cu、Pb的含量,为矿物药的重金属检测提供参考。方法通过对比湿法消解,优选出微波消解作为朱砂样品的前处理方法,结合电感耦合等离子体发射光谱法（ICP-OES）的分析手段,对湖南产的11批朱砂样品中重金属含量进行检测。结果方法的线性相关系数为0.999 8～1.000 0,检出限为0.18～5.54μg·L^-1,RSD为0.55%～3.20%,回收率为84.30%～108.36%,经方法学验证适合同时测定朱砂中Cd、Cr、Cu、Pb的含量。结论该方法简便、准确,可同时检测朱砂中重金属Cd、Cr、Cu、Pb的含量。     

H2S气体分子及相关药物研究进展

硫化氢（hydrogen sulfide,H2S）作为新型的气体信号分子,广泛参与人体各个系统的调节。已知它在心血管系统、神经系统以及胃肠道系统中具有重要的调节作用。本文对近年来H2S在体内合成与代谢、生理活性、检测手段以及相关药物研发做一综述,为H2S供体型药物的研发与临床治疗提供有价值的参考。