Hung Chen-Road
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 70101, China.
World J Gastroenterol. 2006 Jan 28;12(4):574-81. doi: 10.3748/wjg.v12.i4.574.
To investigate the role of gastric oxidative stress and nitric oxide (NO) in the formation of gastric hemorrhagic erosion and their protection by drugs in rats with ischemic brain.
Male Wistar rats were deprived of food for 24 h. Under chloral hydrate (300 mg/kg) anesthesia, bilateral carotid artery ligation was performed. The pylorus and carotid esophagus of the rats were also ligated. The stomachs were then irrigated for 3 h with either normal saline or simulated gastric juice containing 100 mmol/L HCl plus 17.4 mmol/L pepsin and 54 mmol/L NaCl. Rats were killed and stomachs were dissected. Gastric mucosa and gastric contents were harvested. The rat brain was dissected for the examination of ischemia by triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal glutathione level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples, were measured.
Bilateral carotid artery ligation produced severe brain ischemia (BI) in rats. An exacerbation of various ulcerogenic parameters and mucosal hemorrhagic erosions were observed in these rats. The exacerbated ulcerogenic parameters were significantly (P<0.05) attenuated by antioxidants, such as exogenous glutathione and allopurinol. These gastric parameters were also improved by intraperitoneal aminoguanidine (100mg/kg) but were aggravated by N(G)-nitro-L-arginine-methyl ester (L-NAME: 25 mg/kg). Intraperitoneal L-arginine (0-500 mg/kg) dose-dependently attenuated BI-induced aggravation of ulcerogenic parameters and hemorrhagic erosions that were reversed by L-NAME.
BI could produce hemorrhagic erosions through gastric oxidative stress and activation of arginine-nitric oxide pathway.
探讨胃氧化应激和一氧化氮（NO）在缺血性脑损伤大鼠胃出血性糜烂形成中的作用以及药物对其的保护作用。
雄性Wistar大鼠禁食24小时。在水合氯醛（300mg/kg）麻醉下，进行双侧颈动脉结扎。同时结扎大鼠幽门和颈段食管。然后用生理盐水或含100mmol/L盐酸、17.4mmol/L胃蛋白酶和54mmol/L氯化钠的模拟胃液对胃进行灌注3小时。处死大鼠并解剖胃。收集胃黏膜和胃内容物。解剖大鼠脑，采用氯化三苯基四氮唑染色法检查缺血情况。测量胃溃疡形成参数的变化，如胃黏膜谷胱甘肽水平降低、胃酸反向弥散增强、黏膜脂质过氧化物生成、组胺浓度、胃腔内血红蛋白含量以及胃样本中的黏膜糜烂情况。
双侧颈动脉结扎导致大鼠严重脑缺血（BI）。在这些大鼠中观察到各种溃疡形成参数加重和黏膜出血性糜烂。抗氧化剂如外源性谷胱甘肽和别嘌呤醇可显著（P<0.05）减轻这些加重的溃疡形成参数。腹腔注射氨基胍（100mg/kg）也可改善这些胃参数，但N(G)-硝基-L-精氨酸甲酯（L-NAME：25mg/kg）会使其加重。腹腔注射L-精氨酸（0-500mg/kg）剂量依赖性地减轻BI诱导的溃疡形成参数加重和出血性糜烂，而L-NAME可逆转这种作用。
脑缺血可通过胃氧化应激和精氨酸-一氧化氮途径的激活导致出血性糜烂。
