卤虫卵油脂肪酸组成分析及α-亚麻酸含量测定

目的采用毛细管气相色谱法分析卤虫卵油的脂肪酸主要组成并建立测定卤虫卵油中α-亚麻酸含量的方法。方法采用DB-WAX毛细管柱;程序升温:起始温度150℃,升温速率3℃.min-1,结束温度240℃,保持10 min;氢焰离子化检测器温度250℃。结果卤虫卵油中不饱和脂肪酸占总脂肪酸质量分数超过70%,其中油酸、α-亚麻酸质量分数分别为26.9%、27.7%。α-亚麻酸甲酯质量在0.719～3.60μg内线性关系良好(r=0.999 8,n=5),平均回收率为101.6%,RSD=2.3%。结论毛细管气相色谱法可作为卤虫卵油α-亚麻酸的含量测定方法。     

Treatments and compositions targeting α-synuclein: a patent review (2010-2016)

Introduction: Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson’s disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments.

Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization.

Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.     

不同产地槐米炮制前后主成分的含量变化对α－葡萄糖苷酶活性抑制的影响

目的：比较研究10批不同产地槐米炒制前后对槐米中芦丁,槲皮素的含量变化及其对α－糖苷酶活性抑制作用的影响。方法对10批不同产地的槐米药材分别进行炒制,采用高效液相色谱法分别测定各槐米药材提取液中芦丁和槲皮素含量;以对硝基苯酚－β－1,4－葡萄糖苷（ pNPG）为底物,阿卡波糖为阳性对照,测定各槐米药材提取液对α－葡萄糖苷酶活性抑制率,比较了芦丁和槲皮素含量变化对α－葡萄糖苷酶的抑制活性的影响。结果经过炒制后,10批槐米炒制品中的芦丁含量均有所降低,而槲皮素含量则明显升高;槐米炒制品对α－糖苷酶活性抑制作用均优于生品。结论不同产地槐米炮制后,由于槲皮素含量的普遍升高,导致了槐米炒制品对α－葡萄糖苷酶活性抑制作用升高,表明槲皮素在对α－糖苷酶抑制活性起着重要作用。在治疗糖尿病疾病时选用炒制槐米更为合理。     

大鼠腹膜粘连的病理学特征及血清中IL-6、TNF-α的变化

目的探讨大鼠腹膜粘连的病理学特征及血清中白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化。方法将40只SD大鼠随机分成对照组(n=8)和创伤粘连组(n=32)。对照组抽取其静脉血并取其回盲部组织;创伤粘连组分4组,每组8只,分别于术后1、3、5、7天抽取其静脉血和回盲部粘连组织;检测其TNF-α、IL-6,并观察其回盲部组织的病理改变。结果创伤粘连组1周内有明显的炎症反应,局部以纤维组织增生为主,血清中IL-6和TNF-α明显升高(P<0.05)。结论腹膜粘连以纤维组织增生为其病理学特征,细胞因子可能在腹膜粘连形成中发挥一定作用。     

Prostaglandin-versus alpha-adrenoceptor-mediated control of sympathetic neurotransmitter secretion in guinea-pig isolated vas deferens

Noradrenaline (NA) secretion of isolated superfused guinea-pig vas deferenswas studied by determination of total field stimulation-induced efflux of tritium, after preincubation with ³H-l-NA. The medium contained optimal concentrations of desmethylimipramine and normetanephrine to block local rebinding of free NA. Further addition of the two chemically different inhibitors of prostaglandin synthetase, 5,811,14 eicosatetraynoic acid or indomethacin, consistently enhanced the nerve stimulation-induced output of tritium at a frequency of 5/sec, but not at 10/sec. The α-adrenoceptor blocking agent, phenoxybenzamine further strongly elevated nerve stimulation-induced output of tritium. This rise was abolished by low concentrations of exogenous prostaglandin E₂. The results show that sympathetic neurotransmitter secretion in the guinea-pig vas deferens, during low frequency stimulation, is restricted by local formation of prostaglandin E. However and in addition, neurotransmitter secretion appears to be restricted by an α-adrenoceptor-mediated mechanism, which does not appear to depend on endogenous prostaglandin E as a chemical mediator.     

中风胶囊对脑出血大鼠神经功能、脑组织细胞凋亡及肿瘤坏死因子-α的影响

目的探讨中风胶囊对脑出血大鼠神经功能、脑组织细胞凋亡及肿瘤坏死因子-α（TNF-α）的影响。方法选取SD大鼠104只,随机分为5组,即正常组8只,模型对照组、假手术组、中风胶囊大剂量组、中风胶囊小剂量组各24只,后4组按手术后处死时间随机分别分为1、37、d组,每组8只。采用自体血注射法制作大鼠实验性脑出血模型。模型对照组在造模后自由饮食;中风胶囊大、小剂量组在造模后分别给予中风胶囊2.7、1.8 g/（kg.d）灌胃;假手术组操作同模型对照组,但只进针,不注射自体血,术后自由饮食;正常组自由饮食,不做特殊处理。各组分别于第1 d（24 h）、第3 d（72 h）和第7 d进行神经功能评分,随后处死取出脑组织标本,分别采用末端脱氧核糖核酸转移酶介导的缺口末端标记法（TUNEL法）和免疫组化链霉菌抗生物素蛋白-过氧化物酶（SP）法测定血肿周围细胞凋亡和血肿周围TNF-α蛋白表达。结果各组第1、3、7 d神经功能评分、TUNEL阳性细胞比例及TNF-α阳性细胞比例均低于模型对照组（P〈0.01）;中风胶囊大剂量组第37、d神经功能评分、TUNEL阳性细胞比例及TNF-α阳性细胞比例均低于中风胶囊小剂量组（P〈0.05）,中风胶囊大剂量组第1 d TUNEL阳性细胞比例低于中风胶囊小剂量组（P〈0.01,P〈0.05）;中风胶囊大剂量组第7 d神经功能评分、TUNEL阳性细胞比例及TNF-α阳性细胞比例均低于本组第1d（P〈0.01,P〈0.05）。结论中风胶囊能促进脑出血急性期大鼠神经功能恢复,降低脑组织中TNF-α蛋白的表达,从而抑制细胞凋亡,具有减轻炎症及脑组织损伤的作用。     

Effects of estradiol and progestogens on tumor-necrosis factor-alpha-induced changes of biochemical markers for breast cancer growth and metastasis

Background. Epidemiological data suggest an enhanced breast cancer risk during estrogen/progestogen therapy as compared to estrogen monotherapy in postmenopausal women. The underlying mechanism, however, still remains unknown. Estrogens are known to be mitogenic agents for benign and cancerous breast epithelial cells whereas the role of progestogens is unclear. Tumor-associated macrophages play a crucial role in tumor growth and metastasis due to the synthesis of various cytokines such as tumor necrosis factor-α (TNF-α), which can stimulate the synthesis of proliferative and angiogenic factors in tumor cells. In an in vitro model we investigated the influence of estradiol and estradiol/progestogens combinations on the changes of TNF-α- induced markers.

Methods. MCF-7 cells, a human estrogen- and progesterone-receptor-positive human breast cancer cell line, were used for the experiments. Estradiol (E₂), at a concentration of 0.1 nM, and the progestogens progesterone (P), norethisterone (NET) and medroxyprogesterone acetate (MPA), each at concentrations of 0.01 to 1 μM, were tested alone and in combination. The cells were incubated for 4 days and the markers monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured in the supernatant by enzyme-linked immunosorbent assay.

Results. E₂ in combination with TNF-α elicited significant increases in MCP-1 and VEGF concentrations compared with TNF-α alone. For the progestogens alone an increase of MCP-1 was observed for NET, whereas MPA induced a decrease. An increase of VEGF was observed for all progestogens, the effect being greatest for MPA. No changes were found for MMP-9. In combinations with E₂, the E₂-induced increase of MCP-1 was reduced by NET and MPA and the increase of VEGF was diminished by P and NET, but not by MPA. The E₂-induced decrease of MMP-9 was not antagonized by P and NET, but completely abolished by MPA.

Conclusion. Our results indicate that E₂ may have a stimulating effect on pre-existing tumor growth and metastasis. This effect seems to be influenced by progestogens in a different manner. Thus the choice of progestogen addition to estrogen therapy may be important, especially since different effects can occur in the case of pre-existing tumor cells.     

法舒地尔对敌敌畏中毒大鼠急性肺损伤时血浆肿瘤坏死因子α和白细胞介素-6水平的影响

目的：探讨法舒地尔（Fasudil）对敌敌畏中毒大鼠急性肺损伤时血浆肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）水平的影响。方法：Sprague Dawley大鼠30只,随机分成对照组、敌敌畏（dichlorvos,DDVP）中毒组、法舒地尔干预组3组,每组10只,均予以气管切开接呼吸机辅助通气。6h后留取血样用酶联免疫吸附分析（ELISA）法测血浆TNF-α、IL-6水平。取左肺下叶组织,HE染色观察病理学改变。结果：与对照组比,中毒组和干预组大鼠血浆TNF-α、IL-6水平均显著升高（P〈0.01）,肺组织HE染色有炎症细胞浸润;与中毒组比,干预组TNF-α、IL-6升高程度显著降低（P〈0.05）,肺损伤程度较轻。结论：法舒地尔能降低敌敌畏中毒大鼠血浆TNF-α、IL-6水平,能显著减轻肺损伤的病理损害,对大鼠敌敌畏中毒性急性肺损伤有明显的保护作用。     

黄芪多糖对实验性阿弗他溃疡模型大鼠血清TNF-α的影响

目的：探讨TNF-α与复发性阿弗他溃疡（recurrent aphthous ulcer,RAU）发病机制的关系以及观察黄芪多糖（astragalus polysaccharide,APS）对RAU模型大鼠血清中TNF-α含量的影响。方法：通过免疫方法建立SD大鼠RAU动物模型,将大鼠随机分为5组：正常对照组（A）、阴性对照组（B）、APS低（C）、中（D）、高（E）剂量组。灌胃治疗20d后运用酶联免疫吸附试验（ELISA）检测各组SD大鼠血清中TNF-α的表达水平,并提取大鼠口腔黏膜做组织病理学观察。结果：阴性对照组（B）RAU大鼠血清中TNF-α的表达水平显著高于正常对照组（A）（P〈0.05）,连续灌胃20d后,APS各治疗组（C～E）大鼠血清中TNF-α的含量下降,较阴性对照组（B）有显著性差异（P〈0.05）,且高剂量（300mg/kg）APS对TNF-α表达水平的抑制作用较中（200mg/kg）、低（100mg/kg）剂量APS明显。结论：RAU发病可能与血清中TNF-α的表达异常有关,而体内应用APS可以通过剂量依赖方式有效地抑制RAU大鼠血清中TNF-α的表达。     

Protective effects of α-tocopherol against oxidative stress related to nephrotoxicity by monosodium glutamate in rats

Context: Chronic oral intake of high doses of monosodium glutamate (MSG) could be harmful to tissues and organs. Oxidative stress enhances membrane damage by lipid peroxidation and alterations of antioxidant enzymes, which affects the functional activity of organs. Antioxidant vitamins have the capacity to regulate the oxidative stress related functional and pathological processes.

Objective: In this study, the protective role of α-tocopherol against MSG-induced nephrotoxicity was analyzed. Materials and methods: MSG (4?g/kg) was given orally to female wistar rats for a period of 180 days. Renal function parameters (urea, uric acid, and creatinine), lipid peroxidation markers (malondialdehyde and conjugated dienes), antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, and reduced glutathione), and histopathology were investigated. All tests were done in rats treated with MSG and at two different doses of α-tocopherol (100 and 200?mg/kg).

Results: Oral exposure of MSG significantly increased renal function markers, lipid peroxidation byproducts, and altered antioxidant system. Moreover, the kidney showed congested glomeruli, tubular swelling, capillary congestion and microhemorrhages in stromal areas of the tubules. Co-administration of MSG and α-tocopherol (200?mg/kg) significantly reduced the oxidative damage compared with MSG-treated group and also restored the normal renal function.

Discussion: The results indicated that oxidative stress was involved in MSG-induced functional and pathological changes in the kidney. α-tocopherol modulates the functional disorder and maintains the normal architecture of renal tissue by reducing oxidative stress.

Conclusion: The α-tocopherol may be a potent protective agent in combating MSG-induced renal toxicity.