| 1.Background and ObjectivesNoncommunicable diseases (NCDs), mainly cardiovascular diseases, diabetescancers and chronic respiratory diseases, are responsible for about63%of all deathsworldwide. According to the《The World health statistics2012》, it was released on16May2012, the one in three of all adults worldwide have raised blood pressure and theone in ten of all adults have suffered from diabetes.The major target organs of hypertension are heart，blood vessels and kidney.Vascular damage is systemic. Nearly all the organs and tissues have varying degreesof involvement in general. Recent epidemiological studies indicated that theprobability of having diabetes in patients with hypertension compared to the normalpopulation is2-3times higher, which show that the pancreas may also be affected byhypertension in some degree. Most hypertension patients may take nitrates as acombine medicine during the course of disease. Nitrate has been known as NO donorin vitro. Kaneto et al found that the apoptotic features in the pancreatic β-celllinesof hamster after given a high concentration of NO donor. But study on exogenous NOdonor in vivo to the islet function and islet β-cell apoptosis was few.The experimental subjects were Spontaneously hypertensive rats(SHR) andWistar rats. By Using Isosorbide Mononitrate (ISO) as exogenous NO donor, wecompare the expression of apoptotic gene, anti-apoptotic gene and its proteins to observe the damage of β cells, and to investigate the relationship betweenhypertension and diabetes and to explore the effect of ISO on the islet function in therats with hypertension. This study may provide new ideas to help understand thereasons for why the patient with hypertension prone to diabetes.2.Materials and Methods2.1Grouping16-weeks-old male SHR and Wistar rats were divided into6groups in thisexperiment. Each kind has30rats. Those rats had free access to tap water throughoutthe experiments.High fat&high sugar (HFHS)or normal food were given accordingthe group.2.2Islet Function and Gross MorphologyAn intravenous glucose tolerance test (IVGTT) and Intravenous insulin releasingtest (IVIRT) was performed after12-week adaptively feeding in order to observe theislet function. Besides, the pancreas had been taken for HE staining. The content ofNO in the pancreatic tissue were examined by observing nitrate reductase; Thecontent of iNOS were examined by colorimetry.2.3Apoptosis-related Genes DetectionPCR and Western blot had been employed to measure the expression of geneBcl-2and bax and its protein.2.4Statistical AnalysisP <0.05was considered as statistically significant.3.Results3.1Pancreatic Gross MorphologyThe islet mass of SHR rat was greater than that of Wistar rats. A few red bloodcells could be seen in the pancreatic islets of SHR rat, especially in ISO gavagegroup(S-ISO group), but there was no obvious abnormality in islet structure.3.2IVGTT and IVIRTThe fasting glucose(FBG) and fasting insulin(FINS) were no difference betweenSHR rats and Wistar rats (P>0.05); The FBG, FINS and insulin resistance (IR) valuesin SHR rat were higher than that in the Wistar rat after HFHS intervention, thedifference was statistically significant (P <0.05).The blood sugar of SHR group with ISO gavage is higher than the other groups of rats at0min,5min,10min,30minduring the IVGTT, IR was more severe. The sugar level showed the differencebetween high-fat and high-sugar diet and ordinary diet in Wistar rats, but there was nosignificant differences between S-ISO group and physiological saline gavagegroup(saline group) at IVGTT,IVIRT and IR (P>0.05).3.3Levels of NO and iNOS in IsletThe levels of NO and iNOS in pancreatic tissue were higher in SHR group withISO than that in the corresponding Wistar group, the differencec were statisticallysignificant (P <0.05). The levels of NO and iNOS in S-ISO group were higher thanthe saline group. Such differences were not observed in Wistar rats. Comparisonbetween the same type of rats, NO and iNOS in HFHS group was higher than thenormal diet group, the difference was statistically significant (P <0.05).3.4Apoptosis-related Genes ExpressionCompared with the normal diet group, the expression of Bcl-2of HFHS group inpancreatic tissue decreased, Bax expression increased, Bcl-2/Bax ratio decreased, thedifference was statistically significant (P<0.05). In addition, the Bcl-2/Bax ratio in theS-ISO group is lower than that in the saline group, which indicated that the nitricoxide donor lead to apoptosis in pancreatic β cell by increasing the content of NOin pancreatic tissue.4.Conclusions4.1High-fat and high-sugar diet can successfully copy the IR model, and the IRwas more apparent in SHR;4.2ISO,especially in SHR, has an bad impact on glucose metabolism and insulinresistance;4.3ISO can reduce the Bcl-2/Bax ratio and increase apoptosis of islet β cell inSHR. |
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