Gastric mucosal damage in water immersion stress:Mechanism and prevention with GHRP-6

AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious(anesthetized) WRS,simple restraint(SR),free swimming(FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal(IP) or intracerebroventricular(ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm 2 vs normal control 0.0 ± 0.0 mm 2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature(lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm 2 vs WRS at 23 ℃ 81.8 ± 6.4 mm 2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.

Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes

Dear Editor,Obesity is caused by an imbalance between energy intake and expenditure,and has become a global epidemic with over 650 million adults affected.Adipose tissues in mammals are composed of white adipose tissue(WAT)and classical brown adipose tissue(BAT),and their balance is highly related to the occurrence of obesity.The browning of white adipocytes results in“beige”or“brite”adipocytes,which appear functionally similar to classical brown adipocytes,and can be detected in WAT deposits of animals that have been exposed to cold or other inducers(Fu et al.,2015).

Pingwei capsules improve gastrointestinal motility in rats with functional dyspepsia

OBJECTIVE: To investigate the mechanism of Ping-wei capsules(PWC) in improving gastrointestinal m otility in rats with functional dyspepsia(FD).METHODS: We established an FD model by stimu-lating semi-starvation rats via tail damping, provo-cation, and forced exercise fatigue. The FD model group was further divided into five groups accord-ing to the treatment received: normal saline, dom-peridone, low-dose PWC, mid-dose PWC, or highdose PWC. The effect of PWC on FD was evaluated by measuring gastrointestinal motility. Changes in leptin and cholecystokinin(CCK) were detected through enzyme-linked immunosorbent assay, re-verse transcription-polymerase chain reaction, and immunohistochemistry.RESULTS: PWC significantly increased gastrointesti-nal m otility in FD rats. Furthermore, PWC signifi-cantly increased CCK m RNA and protein concentra-tions in the duodenum and antrum, decreased leptin protein concentrations in the duodenum, an-trum, and hypothalamus, and decreased CCK pro-tein concentration in the hypothalamus.CONCLUSION: PWC improves gastrointestinal mo-tor function in FD rats by decreasing the leptin con-centration in serum and the brain-gut axis, and by increasing the CCK concentration in gastrointesti-nal tissue. Our findings help to elucidate the mech-anism of FD and provide further insight into the pharmacokinetics of PWC.