Study On Weight Gain As An Effect Of Diltiazem Treatment

The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist,on gastrointestinal function, food intake and growth promoting,and also to study themechanism of diltiazem.In the Exp1:. Rats were intragastrically administered with diltiazem solution (daily16mg/kg,30mg/kg or80mg/kg,30d), and the rats with saline as control. To detect the effectsof diltiazem on food intake and body weight, the average daily food intake and body weightwere recorded, and the serum metabolic hormones of plasma growth hormone (GH) andneuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometerand the modified Mett’s method, the effects of diltiazem on rat’s gastrointestinal function andpepsin activity were tested, respectively. In addition, the gastric juice’s acidity of rats wasdetected by Titration and the secretion amount was calculated. The results showed that thefood intake and body weight were maximally promoted by diltiazem at the dose of30mg/kgdaily (30d). The average daily food intake（28.06±2.34) and body weight(11.51±1.44)were significantly increased,which compared with the control group respectively((18.73±1.03，5.59±0.98);and the serum concentrations of NPY(447.74±79.13)and GH (5.55±2.09)in medium dose were also remarkably increased in diltiazem-treated groups compared withthose in control group(322.60±16.40，3.40±0.63). The results also showed that the gastricemptying rate（59.5±11.3）, gastric acid secretion（282.89±35.67） and the activity of pepsin（546.75±103.66）were significantly increased in diltiazem-treated group compared withthose in control group（27.1±7.3，148.12±24.51，229.99±64.72）. These resluts suggested thatdiltiazem induced enhancement of eating,in the same time,it could also stimulate thegastrointestinal function and regulate growth of ratIn the Exp2:As the ghrelin receptor agonist,diltiazem could regulate growth of rats,andthese effects whether through the GHSR?For this conjecture,we did the following experiment.The mice were intracerebroventricular injection (i.c.v) of diltiazem and the antisenseoligodeoxynucleotides (ODNs) at different concentrations, the mice with saline as control,todetect the effect on food intake of mice.after intracerebroventricular injection,Theneuropeptide Y(NPY) in hypothalamus and growth hormone(GH) in pituitary were further studied by immunohistochemistry SP method to investigate the expression level.The resultsshowed that the food intake was maximally promoted by diltiazem at the dose of3nmol，Thefood intake（5.063±0.088）significantly increased，which compared with the N.S group（2.571±0.285）.the result of immunohistochemistry also showed that the expression level ofNPY（211.503±3.544）and GH（203.12±5.026） were increased compared with the N.S group（213.55±6.967，242.77±0.625）respectively;.the i.c.v injection of ODNs of growth hormonesecretagogue receptor(GHSR) inhibite the food intake significantly,Moreover,the expressionlevel of GH in pituitary was reduced,but no effect on the NPY consentration.After both i.c.vinjection of Diltiazem(3nmol)and ODNs(4nmol),the food intake of mice,compared withdiltiazem group,was reduced,but there was no significant difference with the N.S group,Theexpression level of GH and NPY was apparently inhibited,which compared with the diltiazemgroup.these date indicated that GHSR may play key roles in regulating the physiologicalfunction of diltiazem.These resluts suggest that diltiazem induced enhancement of eating,increaed the weightof rat,in the same time,it could also stimulate the gastrointestinal function and regulategrowth,and could promote the expression of GH and NPY.