OBJECTIVETo explore the possible angiogenesis mechanism of Huazhuo Jiedu Hewei Recipe (HJHR) in preventing and treating precancerous lesions of gastric cancer (PLGC).

METHODSTotally 66 Wistar rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the retinoic acid (RA) group, the high dose HJHR group, the middle dose HJHR group, the low dose HJHR group, 11 in each group. PLGC model was duplicated by inserting a spring with Helicobacter. Corresponding medicines were administered to rats in each medicated group once daily by gastrogavage, 2 mL each time for 12 successive weeks. The effect of HJHR on hypoxia induced factor (HIF-1alpha) and vascular endothelial growth factor (VEGF) of PLGC in chronic atrophic gastritis (CAG) rats' gastric mucosa was observed by immunohistochemical assay and Western blot method.

RESULTSCompared with the normal control group, the expression of VEGF and HIF-1alpha increased in the model group (P < 0.05). Compared with the model group, the expression of VEGF and HIF-1alpha decreased in each medicated group (P < 0.05). Besides, they were lower in the high and middle dose HJHR groups than in the RA group and the low dose HJHR group (P < 0. 05). There was no statistical difference between the low dose HJHR group and the RA group (P > 0.05).

CONCLUSIONHJHR could prevent and treat PLGC of CAG rats possibly through decreasing the expression of HIF-1alpha and VEGF in a dose-dependent manner.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; metabolism ; Gastritis ; metabolism ; microbiology ; Helicobacter ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Neovascularization, Pathologic ; Precancerous Conditions ; blood supply ; drug therapy ; metabolism ; Rats ; Rats, Wistar ; Stomach Neoplasms ; blood supply ; drug therapy ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

The present study aimed to investigate the protective effect and mechanism of hydrogen sulfide donor NaHS administration against gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) in rats. GI-R injury was induced by clamping the celiac artery of adult male SD rats for 30 min and followed by reperfusion for 1 h. The rats were randomly divided into sham group, GI-R group, NaHS group, glibenclamide group and pinacidil group. Gastric mucosal damage was analyzed with macroscopic injured area, deep damage was assessed with histopathology scores, and the hydrogen sulfide concentration in plasma was determined by colorimetric method. The results showed that pretreatment of NaHS significantly reduced the injured area and deep damage of the gastric mucosa induced by GI-R. However, NaHS did not significantly alter the levels of hydrogen sulfide in plasma 14 d after NaHS administration. The gastric protective effect of NaHS during reperfusion could be attenuated by glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker. However, K(ATP) opener pinacidil inhibited the GI-R-induced injury. These results suggest that exogenous hydrogen sulfide plays a protective role against GI-R injury in rats possibly through modulation of K(ATP) channel opening.
Animals ; Gastric Mucosa ; pathology ; Hydrogen Sulfide ; metabolism ; Ischemic Preconditioning ; methods ; KATP Channels ; metabolism ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Stomach ; blood supply ; Sulfides ; pharmacology

OBJECTIVETo investigate the regulatory effect of jianpi jiedu Recipe (JJR) on the microvessel density (MVD) and cyclooxygenase-2 (COX-2) in long-term infection of Helicobacter pylori induced gastric cancer of C57BL/6 mice, thus providing experimental bases for its treatment of the H. pylori correlated gastropathy.

METHODSC57BL/6 mouse gastric cancer model induced by H. pylori infection was established by gastrogavage of H. pylori standard strain SS1. Mice were divided into the control group, the model group, low dose JJR group, and the high dose JJR group, 40 in each group. Mice were sacrificed after 72-week medication. Changes of the gastric mucosa MVD of mice in each group were detected by immunohistochemical method. Expressions of COX-2 mRNA and protein were detected by Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method.

RESULTSThe occurrence rate of gastric cancer in the control group, the model group, the low dose JJR group, and the high dose JJR group was 0, 22.2%, 11.1%, and 10.0%, respectively. The gastric mucosa MVD (number/cm2) of mice in each group was 2.50 +/- 1.54, 18.56 +/- 2.62, 14.61 +/- 3.60, and 7.39 +/- 1.75, respectively. The gastric mucosa MVD in the model group increased more obviously than that in the control group (P < 0.01). The gastric mucosa MVD significantly decreased in the low dose JJR group and the high dose JJR group (P < 0.01). Expressions of COX-2 mRNA and protein in the model group increased more obviously than those in the control group (P < 0.01). Low dose JJR and high dose JJR could decrease their expressions in a dose dependent manner.

CONCLUSIONSH. pylori infection could increase the gastric mucosa MVD of C57BL/6 mice and promote COX-2 expressions, which might play a promoting effect in the incidence of H. pylori induced gastric cancer. JJR could decrease the gastric mucosa MVD and inhibit COX-2 expressions, which might be one of its important mechanisms of preventing and treating gastric cancer.

Animals ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gastric Mucosa ; blood supply ; drug effects ; metabolism ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; microbiology

The present study aimed to investigate the protective mechanism of N-acetylcysteine (NAC) against gastric ischemia /reperfusion (GI/R) injury in rats. After intravenous injection (IV) of NAC (150 mg/kg) into femoral vein, the rats were subjected to 30 min of ischemia induced by clamping the celiac artery followed by 60 min of reperfusion. After the gastric mucosal damage index (GMDI) had been calculated, gastric mucosal cell in situ apoptosis was detected by TUNEL method. The protein expression of p-ERK, p-JNK and NF-kappaB, and mRNA expression of TNF-alpha and Caspase-3 in gastric mucosa were evaluated by using Western-blot or RT-PCR, respectively. The results showed that NAC not only attenuated the GI-R injury, but also decreased gastric mucosal cellular apoptosis. Furthermore, NAC increased the protein expression of p-ERK, while inhibited protein expression of p-JNK, NF-kappaB in gastric mucosa. NAC also decreased the expression of TNF-alpha mRNA and Caspase-3 mRNA in gastric mucosa. Capsazepine (CPZ) (400 mg/kg, IV) reversed the protective effect of NAC against GI/R injury in rats. These results suggest that NAC can protect rats against GI/R injury. This protective effect is possibly mediated by the up-regulation of p-ERK and down-regulation of p-JNK and NF-kappaB. In addition, vanilloid receptor subtype 1 may be involved in the protective mechanism of NAC against GI/R injury.
Acetylcysteine ; pharmacology ; Animals ; Apoptosis ; Gastric Mucosa ; pathology ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; prevention & control ; Stomach ; blood supply

BACKGROUNDWe investigated the role in electrical stimulations of paraventricular nucleus (PVN) on gastric mucosal cells and the activity of mitogen-activated protein kinases (MAPKs) family members induced by gastric ischemia-reperfusion (GI-R). And we elucidated the molecular mechanisms of the protection of PVN from GI-R injuries.

METHODSSprague-Dawley rats were divided randomly into 4 groups: Group I, the sham-operated GI-R control group; Group II, the sham-operated electrical stimulations to PVN + sham-operated GI-R control group; Group III, the GI-R group; and Group IV, the electrical stimulations to PVN + GI-R group. In all of the experiments, the PVN was stimulated prior to the induction of GI-R. The GI-R model was established by clamping the celiac artery for 30 minutes to induce ischemia and then was released to allow reperfusion for 30 minutes, 1 hour, 3 hours and 6 hours, respectively. The gastric mucosal cellular apoptosis, proliferation, and the expression and activity of MAPKs protein were observed by immunohistochemistry and Western blotting, respectively.

RESULTSCompared with the GI-R group, the application of electrical stimulations in the PVN significantly depressed gastric mucosal cellular apoptosis and enhanced gastric mucosal cellular proliferation following the 30-minute, 1-hour and 3-hour intervals of reperfusion; it also promoted the activation of p-ERK during the early phase of reperfusion but inhibited the activation of p-JNK1/2 and p-p38 following the 30-minute, 1-hour and 3-hour intervals of reperfusion.

CONCLUSIONSThe protection of PVN against GI-R injuries may attribute to the inhibition of apoptosis and the promotion of the proliferation of gastric mucosal cells during GI-R. This protective effect is mediated by activating the ERK pathway and depressing the JNK, p38 MAPK pathways of the gastric mucosal cells.

Animals ; Apoptosis ; Cell Proliferation ; Electric Stimulation ; Extracellular Signal-Regulated MAP Kinases ; physiology ; Gastric Mucosa ; blood supply ; enzymology ; pathology ; JNK Mitogen-Activated Protein Kinases ; physiology ; MAP Kinase Signaling System ; physiology ; Male ; Paraventricular Hypothalamic Nucleus ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; p38 Mitogen-Activated Protein Kinases ; physiology

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Gastric Mucosa ; blood supply ; pathology ; Hypertension, Portal ; drug therapy ; Male ; Propranolol ; therapeutic use ; Rats ; Rats, Wistar ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVETo study the protective effect of puerarin on stress-induced gastric mucosal injury in rats.

METHODThe model of gastric ulcer was established by restraint plus water-immersion stress in rats. Gastric motility was monitored by the method of "Gas Balloon". Gastric mucosal blood flow was recorded by laser-Doppler flowmetry. Colorimetric method was used to determine the content of NO and ET in gastric mucosal tissue. Meantime the pathologic changes of gastric mucosal was examined.

RESULTPuerarin could significantly attenuated gastric mucosal damage induced by water-immersion stress, inhibited gastric motility, specially decreased the index of gastric motility and percentage of gastric contraction time and numbers of violent contraction. The gastric mucosal blood flow and NO level in gastric mucosal were enhanced, while ET level was reduced by puerarin. The degree of tissue damage in gastric mucosal was also significantly attenuated after administration fo puerarin.

CONCLUSIONPuerarin exerts a significant protective effect on water-immersion stress-induced gastric mucosal damage by relaxing the vessels, increasing NO level in gastric mucosal, increasing regional gastric mucosal blood flow and inhibiting gastric motility.

Animals ; Endothelins ; metabolism ; Female ; Gastric Mucosa ; blood supply ; metabolism ; pathology ; Gastrointestinal Motility ; drug effects ; Isoflavones ; isolation & purification ; pharmacology ; Male ; Nitric Oxide ; metabolism ; Protective Agents ; pharmacology ; Pueraria ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Regional Blood Flow ; drug effects ; Stomach Ulcer ; etiology ; metabolism ; pathology ; Stress, Physiological ; complications

The effect of gastric ischemia-reperfusion (GI-R) on gastric mucosal cellular apoptosis and proliferation was investigated using histological, immunohistochemical methods in Sprague-Dawley rats. The GI-R model was established by clamping the celiac artery for 30 min and reperfusing for 0, 0.5, 1, 3, 6, 24, 48, 72 h, respectively. Mild gastric mucosal injury was induced by ischemia alone. However, the injury worsened and reached the maximum at 1 h after reperfusion, almost simultaneously with the gastric mucosal cellular apoptosis increase and cellular proliferation decrease in gastric mucosa. Then, gastric mucosal cells began to repair by increasing gastric cellular proliferation, which achieved the maximum at 24 h after reperfusion. The mucosal lesions were almost completely repaired at about 72 h after reperfusion. These results indicate that the gastric mucosal injury after GI-R is mainly induced by reperfusion. The damaged gastric mucosa could initiate its repairing mechanism immediately through inhibiting cellular apoptosis and increasing the number of proliferative cells, which substitute the damaged cells gradually. The plerosis almost completes in three days after reperfusion showing a strong self-repair ability of gastric mucosa.
Animals ; Apoptosis ; physiology ; Cell Proliferation ; Female ; Gastric Mucosa ; pathology ; physiology ; Ischemia ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Regeneration ; physiology ; Reperfusion Injury ; physiopathology ; Stomach ; blood supply ; pathology ; physiology

AIMTo observe the degree of gastric mucosal injury following limb ischemia/reperfusion (LI/R), and to investigate the mechanism of gastric mucosal injury and the protection of ischemic preconditioning (IPC) on gastric mucosal injury.

METHODSThe model rats which underwent 4 hours of ischemia and 4 hours of reperfusion of hind limbs were made. Then we respectively observed and determined the histologic lesion score after I/R and IPC + I/R. The gastric barrier mucus in mucus were measured in different groups. The values of MPO, SOD, MDA and XOD in gastric mucosa and the values of MDA, XOD, SOD, LDH in plasma were detected.

RESULTSIn the LI/R group, the histologic lesion score increased significantly. The content of gastric barrier mucus in mucus decreased significantly. The value of MPO, MDA, XOD in gastric mucosa and the values of MDA, XOD, LDH in plasma increased remarkably and SOD activity in gastric mucosa and in plasma decreased. However in the IPC group, the histologic lesion score decreased significantly and the content of gastric barrier mucus in mucus increased significantly and the value of MPO MDA XOD LDH in gastric mucosa or in plasma decreased remarkably and the SOD activity increased compared to LI/R group.

CONCLUSIONLI/R will lead to the development of stress ulcer, oxygen free radicals play an important role in it. IPC can alleviate the damage of gastric mucosa following ischemia/reperfusion of hind limbs. The decrease of OFR is one of the protection mechanism of IPC.

Animals ; Extremities ; blood supply ; Gastric Mucosa ; metabolism ; pathology ; Ischemic Preconditioning ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology

OBJECTIVETo investigate the protective effects of the polysaccharides isolated from ganoderma applanatum (PGA) on gastric mucosal injury in rats and the underlying mechanism.

METHODGastric ulcer was induced by either acetic acid or pylorus ligation in the rats. The level of PGE2 and GMBF, and gastric mucus secretion were examined respectively.

RESULTAfter oral administration of PGA (250-1000 mg x kg(-1)) repeatedly, the level of PGE2 and GMBF were obviously increased in gastric mucosa of rats as compared with the model group. The secretions of both free mucus in stomach and mucus of gastric wall were enhanced apparently by PGA in a dose-dependent manner.

CONCLUSIONPGA could strengthen gastric mucosa barrier by improving the level of PGE2, GMBF and the secretion of gastric mucus, which may be one of the mechanisms underlying the protective effect of PGA on the gastric mucosa during the gastric ulcer.

Animals ; Anti-Ulcer Agents ; administration & dosage ; isolation & purification ; pharmacology ; Dinoprostone ; metabolism ; Dose-Response Relationship, Drug ; Female ; Ganoderma ; chemistry ; Gastric Mucosa ; blood supply ; metabolism ; secretion ; Male ; Mucus ; secretion ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacology ; Rats ; Rats, Wistar ; Regional Blood Flow ; drug effects ; Stomach Ulcer ; metabolism