| Background: Diabetes Mellitu is a chronic metabolic disease which inducesdamage and malfunction of multiple tissues and organs. Diabetes syndrome patientsare becoming commoner around the world as the increase of incidence of DMincreases and decrease of average patient age-group. Over all syndromes, DiabeticNephropathy is the most fatal and commonest. Recent researches have indicated thatthe mechanism of DM is mainly related to glucose metabolism pathway, oxidativestress, and inflammatory cytokines.Low-dose radiation (LDR) has distinct effects from high-dose radiation., and itcould stimulate excitatory effect and introduce adaptive response in living organism.It includes improving immunity and reproductive ability, prolonging life span andpreventing radiational and chemical damage. Recently there are several possiblemechanism for low dose radiation induced hormesis:①Low dose radiation canimprove DNA repair;②Low dose radiation can mediate the expression of manykind of protein;③Low dose radiation can mediate many kind of cell signalingpathways;④Low dose radiation can induce the expression of many kind ofantioxidant enzyme;⑤Low dose radiation can mediate apoptosis.Objective: We have demonstrated that exposure of diabetic mice to LDR at25mGy of X-rays daily for12weeks could significantly attenuate diabetes-induced renalinflammation, oxidative damage and remodeling as well as renal dysfunction.However, the mechanism by which LDR prevents diabetic nephropathy remainslargely unknown. We want to find the main mechanism of LDR on enal protection inType1diabetic mice through our reaserch.Method: Eight weeks old male C57BL/6J mice were used for diabetes modles.Both groups of mice were fasted overnight and then were given by intraperitonealinjection of STZ at60mg/kg body weight daily for6consecutive days or equivalentvolume of the citrate buffer. Blood glucose level was determined using a Freestyleglucometer1week after the last injection of STZ. We considered mice to be diabeticwhen blood glucose was≥12mmol/l. Mice from both diabetic and age-matchedcontrol groups were randomly divided into two groups with and without LDR. Eight mice from each group were euthanized at1,3,6,9, and12h after LDRexposure.Blood serum,urine and kidney tissue were collected for ELISA,WesternBlotting and IHC test.Result:The present study was to explore the possible mechanism by whichLDR prevents diabetes-induced renal damage using the same model as used before.C57BL/6J mice were used to induce type1diabetes with multiple low-dosestreptozotocin. Once hyperglycemia was onset diabetic and age-matched control micewere irradiated with whole-body X-rays at either single25mGy,75mGy or3x25mGy (25mGy daily for3days) and then sacrificed at1–12h. Renal Aktphosphorylation and Nrf2expression were examined with Western blotting andimmunohistochemical staining. In addition, Nrf2transcription function was alsoexamined by determining its down-stream antioxidants, including NQO1, HO-1andSOD. Results showed that LDR at75mGy stimulated Akt phosphorylation andup-regulated Nrf2expression and transcription in diabetic kidneys. Exposure to singleLDR at25mGy did not, but exposure to three LDRs at25mGy (accumulated at75mGy) could provide a similar effect as single LDR at75mGy on the stimulation ofAkt phosphorylation and up-regulation of Nrf2expression and transcription. Theseresults suggest that single75mGy or multiple25mGy of X-rays can stimulate Aktphosphorylation and up-regulate Nrf2expression and transcription function. But alldoses can not stimulate GSK3β phosphorylation and induce GS phosphorylation.Conclusion:In summary, we have demonstrated that single or accumulated75mGy of X-rays can stimulate Akt phosphorylation and up-regulate Nrf2expressionand transcription in diabetic kidneys. It’s useful for clinical research. |
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