| Objective: Nowadays, with the rapid development of the economy andthe acceleration of the industrialization process, non-communicable diseasesinduce more and more threats to human health, the prevalence of diabetesand the the number of diabetes are in sharp rise. Incretins, as a class ofintestinal hormones, released after eating, the release of such hormonesinduce glucose-dependent stimulation of insulin secretion while suppressingglucagon secretion and thus provide new ideas for the human treatment ofdiabetes. The pancreatic effects and other biological effects of GLP-1gradually attracted people’s attention. The GLP-1receptor is expressed inthe pancreas, intestines, nervous system, lung, kidney and heart tissue.GLP-1may play a lipid-lowering, antihypertensive effect, and thus have aprotective effect on the cardiovascular system; enhancing learning andmemory function, protect nerve;play a Kidney protective effect byanti-fibrosis, reducing oxidative stress, reducing urinary protein; inhibitbone resorption, protect bone. Many receptors and the receptor pathwaysand the effectors composed of an extremely complex network of signaltransduction pathways. In this network, Any change may affect the entiresystem, thus causing changes in the corresponding biological effects. Manyfactors can influence cell receptor number and (or) receptor ligand affinitythrough a variety of mechanisms. The receptor levels in human physiologicalstate has a certain correlation with diseases. There is no reports about theexpression of GLP-1R (Glacogon-like Peptide-1Receptor) and PKA(Protein Kinase A PKA, cAMP-dependent protein kinase, referred to askinase A) in the renal tissue of diabetic and osteoporosis animal model.This study was designed to provide experimental evidence and theoreticalbasis for the study of diabetes, osteoporosis, pathogenesis and treatment of diabetic nephropathy and diabetic osteoporosis, explore the GLP-1Rexpression of PKA in rat kidney tissue of diabetes and osteoporosis.Methods:100healthy female Wistar rats (2.5-3months) after feedingfor one week, were randomly divided into four groups:normal control group(sham group, NC group, N=24), ovariectomy group (NOVX group, N=26),diabetic control group (the diabetic sham operation group, DC groupN=24), the diabetes ovariectomy group (DOVX group, N=26). Bodyweight of the rats in the four groups showed no significant difference.Asmall dose of STZ intraperitoneal injection combined with a high fat dietproduced the rat model of diabetes; The bilateral oophorectomy produced therat model of osteoporosis. At4weeks、8weeks、and12weeks afteroperation, four rats were randomly selected from each group, Sacrificed byAnesthesia,separated kidney from each rat and derived renal tissue rapidly,the renal tissues were embedded in paraffin blocks. The expression ofGLP-1R、PKA of the renal tissue in NC group、NOVX group、DC group andDOVX group was detected by immunohistochemistry(IHS). Each set of dataconsistents with Normal distribution, the groups were compared usingunivariate analysis of variance (one-way ANOVA) the SNK method andDunnett’s T3method, P <0.05indicated a statistically significant difference.Results:1The pathology of the kidney in each group(HE staining): theglomerular in NC and NOVX groups is clear, the capillary loops ofglomerular is clear and thin.The number of Endothelial cells and mesangialcells is normal,the renal tubular is normal. In DC and DOVX groups,eosinophilic material within the kidney glomerular capillary and the numberof endothelial cells and mesangial cells increased,the basement layer of renaltubular is thickened.2The expression of GLP-1R in each group: GLP-1R mainly expressed inthe membrane and cytoplasm of the renal tubular epithelial cells. At4w、8w、12w after operation, the expression in NOVX groups and DOVX groups islower than that in control groups; the expression of GLP-1R is decreased along with the time in DC ang DOVX groups.3The expression level of PKA in each group: PKA expressed incytoplasm of the renal tubular epithelial cells. At4weeks after ovariectomy,the expression in NC group is significantly lower than that in NOVX、DC、andDOVX groups; At8weeks after ovariectomy, the expression in DOVX groupis significantly lower than that in NC group; At12weeks after ovariectomy,the expression in NC group is significantly lower than that in DC group.Conclusions:1The expression of GLP-1R in DC and DOVX groups decreases withtime,that maybe releated to the progression of diabetes.2The expression of GLP-1R in NOVX and DOVX groups is lower thancontrol groups, that maybe releated to the progression of osteoporosis.3The trends of PKA and GLP-1R level is not entirely consistent, PKA,as a indicate target protein exist in many signal transductions and there aresome limitations in the reaction of the GLP-1R signaling, more sensitive andspecific indicators Should be explored to reflect the GLP-1signalpathway,or to observe dynamically after experimental intervention. |
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