基于钙离子通道探讨麻黄鞣酸及麻黄等治疗哮喘作用机制研究

目的 :基于钙离子通道探讨麻黄鞣酸及麻黄等治疗哮喘作用机制研究。方法 :60只大鼠随机分为空白组、对照组、模型组、麻黄组、麻黄鞣酸组、麻杏止咳片低剂量组、麻杏止咳片高剂量组。构建哮喘模型后,采用HE染色计算哮喘大鼠支气管横断面单位面积的炎性细胞数以及WAm/Pbm,WAi/Pbm,以评估气道炎症。用免疫组化法及蛋白质免疫印迹法(Western-blot)测定大鼠CACC和T MEMl6A蛋白表达。结果 :(1)炎性细胞数,模型组高于空白组(P<0.01)。与模型组比较,炎性细胞数,鞣酸组、麻黄组、麻杏止咳片低剂量组、麻杏止咳片高剂量组降低(均P<0.01)。WAm/Pbm,WAi/Pbm,鞣酸组下降(P<0.01),麻黄组、麻杏止咳片低剂量组、麻杏止咳片组高剂量组与模型组比较无差异。(2)CACC1在模型组和空白对照组,模型组阳性表达细胞数目多于对照组,强度也高于对照组(P<0.01)。与模型组比,计算其光密度比值,鞣酸组、麻黄组、麻杏止咳片低剂量组、麻杏止咳片组高剂量组比值下调(P<0.01)。CACC4在模型组和空白对照组,模型组阳性表达细胞数目多于对照组,强度也高于对照组(P<0.01)。与模型组比较,计算光密度比值,鞣酸组、麻黄组、麻杏止咳片低剂量组、麻杏止咳片组高剂量组比值下调(均P<0.01)。(3)各组大鼠肺组织中TMEM16A的表达检测结果显示:与空白对照组比较,其余各组大鼠肺组织中TMEM16A的表达水平均显著下调,差异有统计学意义(P<0.01);与模型对照组比较,各治疗组大鼠肺组织中TMEM16A的表达水平均显著上调,差异有统计学意义(P<0.05或0.01);其中麻杏止咳片高剂量组大鼠肺组织中TMEM16A的表达水平上调最为显著。结论 :(1)麻黄鞣酸可以使WAm/Pbm、WAi/Pbm下降,可以改变气道重构。(2)鞣酸组、麻黄组、麻杏止咳片低剂量组、麻杏止咳片高剂量组均可以下调CACC1、CACC4在肺组织中的表达,也都可以上调TMEM16A的表达。

Gastric carcinogenesis

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.