endothelin-1 and Peptic-Ulcer

To explore the therapeutic effects and mechanisms of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers.. One hundred and twenty patients were randomly divided into 6 groups. Another 10 patients as the control group were confirmed with no peptic ulcers by endoscope, but had digestive tract symptoms. The clinical effects were compared among each group after the one month treatment.. The clinical effects of the combination of Jianweiyuyang granules and ranitidine capsules were better than those of western medicine, with improvement in symptoms and syndrome (P < 0.01 to 0.05), but there was not significant difference with the rate of ulcer healing and the Hp clearance among the combination of Jianweiyuyang granules and ranitidine capsules, Jianweiyuyang granules, and ranitidine capsules (P > 0.05). The combination of Jianweiyuyang granules and ranitidine capsules could significantly upregulate the expression of MUCSAC mRNA (P < 0.01), while downregulate the expression of ETAR mRNA (P < 0.01).. There is obvious advantage in treating peptic ulcers by the combination of Jianweiyuyang granules and ranitidine capsules, and its mechanisms may be to protect the gastric mucosal barrier by up-regulating the expression of MUCSAC mRNA and to improve the gastric mucosal blood flow by down-regulating the expression of ETAR mRNA.

Topics: Adult; Capsules; Drug Therapy, Combination; Drugs, Chinese Herbal; Endothelin-1; Female; Gastric Mucosa; Humans; Male; Middle Aged; Mucin 5AC; Mucins; Peptic Ulcer; Phytotherapy; Ranitidine; Receptors, Endothelin; RNA, Messenger

BACKGROUND This study investigated the correlations between acute cerebral hemorrhage complicated with stress ulcer bleeding and corresponding indexes, including the Acute Physiology and Chronic Health Evaluation (APACHE) II score, vascular endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-α), and blood lipid factors. MATERIAL AND METHODS A total of 53 patients with acute cerebral hemorrhage complicated with stress ulcer bleeding were selected as the observation group and 50 patients with simple acute cerebral hemorrhage were selected as the control group. The APACHE II score and the levels of ET-1, TNF-α, and blood lipid factors, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA), were detected and the correlations of were analyzed between the 2 groups of patients. RESULTS The blood lipid index TG, APACHE II score, ET-1, TNF-a, renal function indexes [blood urea nitrogen (BUN) and creatinine (Cr)], mortality rate, hemoglobin, and MDA in the observation group were significantly higher than those in the control group, while HDL-C in the observation group was obviously lower than in the control group (p<0.05). The APACHEII score had positive correlations with TG and TNF-α (r=0.8960, r=0.8563, respectively), while it was negatively correlated with TC, HDL-C, LDL-C, and ET-1 (r=-0.909, r=-0.9292, r=-0.8543, and r=-0.8899, respectively) (p<0.001 in all comparisons). APACHEII score, BUN, and Cr were all risk factors. CONCLUSIONS Stress ulcer in patients with acute cerebral hemorrhage is associated with blood lipid changes and inflammation, which provides clues for the diagnosis and treatment of acute cerebral hemorrhage.

Topics: Adult; APACHE; Cerebral Hemorrhage; Cholesterol, HDL; Cholesterol, LDL; Endothelin-1; Female; Humans; Lipids; Male; Middle Aged; Peptic Ulcer; Risk Factors; Stress, Psychological; Triglycerides; Tumor Necrosis Factor-alpha

To observe the respective effects of intervention either with endothelin (ET) antibody or with ET receptor antagonist on acute stress ulcer (ASU) subsequent to cerebral hemorrhage in rats.. Forty Sprague-Dawley (SD) rats were randomly divided into control group (group A, n=10), model group (group B, n=10), ET antibody (group C, n=10), and ET receptor antagonist group (group D, n=10). Right intracerebral hemorrhage was reproduced by injection of 200 microl autologous venous blood. Normal saline, ET antibody, or ET receptor antagonist was respectively administered intravenously per day for designated group. The rats were sacrificed at 3 days of the experiment. The incidence of ASU and ulcer index were assessed, serum ET-1 level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in serum, Rsvmit (Rsv) and Vvmit (Vv) of cerebral and gastric mucosa were measured, and pathological examination of the cerebral tissue and gastric mucosa was performed with light microscopy and electron microscopy.. In group B, serum ET-1 level did not changed. MDA content were markedly increased in serum, cerebral and gastric mucosa, SOD activity were markedly decreased, cerebral water content were markedly increased; Rsv in neuron and gastric parietal cell, Vv in gastric parietal cell both were markedly decreased (P<0.05 or P<0.01). ASU was only observed in group B (the incidence was 30%, ulcer index was 15). It was not observed in other groups. Compared with group B, MDA content were significantly decreased, and SOD activity were significantly increased in serum, cerebral and gastric mucosa in groups C and D, cerebral water content in group C were dramatically decreased (all P<0.01), but these were not statistically different between groups C and D. Rsv and Vv in neuron and gastric parietal cell in groups B, C and D were not statistically different, and serum ET-1 level were not statistically different among the groups (all P>0.05).. Intervention of ET antibody and ET receptor antagonist can both reduce occurrence and development of ASU subsequent to cerebral hemorrhage in rats.

Topics: Animals; Anti-Ulcer Agents; Antibodies; Brain; Cerebral Hemorrhage; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Gastric Mucosa; Male; Malondialdehyde; Peptic Ulcer; Rats; Rats, Sprague-Dawley; Stomach; Superoxide Dismutase

We investigated the role of xanthine oxidase-derived oxygen radicals in the development of endothelin-1-induced gastric ulcer. Mucosal lipid peroxidation showed a peak 24 h after injection, while gastric mucosal haemodynamics were fully restored 26 h after endothelin-1 injection. Allopurinol and oxypurinol, but not superoxide dismutase or catalase, protected the gastric mucosa 24 h after endothelin-1 injection. Oxypurinol antagonized both the vasoconstrictor effect of endothelin-1 and the decrease in gastric ATP. All treatments on the second day after endothelin-1 injection significantly reduced gastric mucosal damage. Xanthine oxidase-derived oxygen radicals contributed largely to the exacerbation but they did not mediate the onset of endothelin-1-induced gastric ulcer. Pretreatment with probucol (500 mg/kg, p.o.) also protected the gastric mucosa from endothelin-1-induced mucosal injury by its antioxidant activity. Oxypurinol was gastroprotective through its vasoactive and energy saving actions. The haemodynamic background of endothelin-1-induced gastric ulcer consists of long lasting ischaemia and subsequent "reperfusion" which may be responsible for the late burst of oxygen radicals.

Topics: Adenosine Triphosphate; Aldehydes; Allopurinol; Animals; Catalase; Deferoxamine; Disease Progression; Endothelin-1; Gastric Mucosa; Male; Malondialdehyde; Oxypurinol; Peptic Ulcer; Probucol; Rats; Rats, Wistar; Regional Blood Flow; Superoxide Dismutase; Superoxides; Vasoconstriction; Xanthine Oxidase

Peptic ulcer in the human stomach causes localized destruction of the gastric wall, which may be associated with focal vascular insufficiency. Endothelin-1, an extremely potent vasoconstrictor peptide, modulates regional blood flow in the vasculature of stomach, suggesting a role for endothelin-1 in peptic ulcer. We examined the relationship among endogenous plasma and mucosal endothelin-1 concentrations and the severity and area of ulcer in 19 patients with gastric ulcers and eight healthy adults. Endothelin-1 concentrations were measured by enzyme immunoassay in plasma and gastric mucosal specimens from ulcer margins, corpus, and antrum. The severity and area of ulcer were assessed endoscopically. Plasma endothelin-1 concentrations in active (P < 0.01 compared with normal) and healing (P < 0.05) stages of ulcer were significantly greater than those in normal subjects. Plasma endothelin-1 concentrations, but not mucosal endothelin-1 concentrations in the ulcer margin, were significantly associated with the severity of the ulcer. There was a significant positive correlation between plasma endothelin-1 concentrations and area of ulcer (r = 0.70, P < 0.01). In conclusion, locally increased endothelin-1 may be an important mediator contributing to the pathogenesis of peptic ulcer.

Topics: Adult; Endothelin-1; Female; Gastric Mucosa; Humans; Immunoenzyme Techniques; Male; Middle Aged; Peptic Ulcer