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Aim:Several epidemiological studies have suggested that treatment with angio-tensin Ⅱ type 1 receptor blocker provided a risk reduction of developing type 2diabetes.The aim of this study was to investigate whether and how chroniccandesartan treatment can attenuate the deleterious influence of the hyperactivelocal intra-islet renin-angiotensin system in the diabetes state.Methods:Eight-week-old db/db mice were randomized to candesartan 1 mg/kg,candesartan 10mg/kg,manidipine 10 mg/kg,or placebo via gavage for 6 weeks.Their age-matchednondiabetic littermates db/m mice were treated with placebo and acted as nondia-betic controls.After 6 weeks’ treatment,an intraperitoneal glucose tolerance test,immunohistochemical staining of oxidative stress markers,insulin,CD31,azanstaining and an electron microscopy observation were performed.Results:Chroniccandesartan treatment provided an improvement of glucose tolerance,and greatlyrescued islet β-cell mass.Candesartan treatment also notably decreased stainingintensity of oxidative stress markers,as well as attenuating intra-islet fibrosis andimproving blood supply in the islet.In the electron microscopy observation,candesartan-treated animals exhibited improved granulation and less remarkableendoplasmic reticulum and Golgi bodies;furthermore,candesartan treatment greatlyrelieved the swelling of mitochondria to nearly normal.Both the benefits of reduc-ing oxidative stress and ultrastructure protection were in a dose-dependent andblood pressure-independent manner.Conclusion:After diabetes was initiated,candesartan treatment could not reverse the state of diabetes,but it effectivelyimproved glucose tolerance and protected β-cell function by attenuating oxida-tive stress,islet fibrosis,sparsity of blood supply and ultrastructure disruption ina dose-dependent and blood pressure-independent manner.
Aim: Several epidemiological studies have suggested that treatment with angio-tensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. The AIM of this study was to investigate whether and how chronic candesartan treatment can attenuate the deleterious influence of the hyperactive intraocular intra- islet renin-angiotensin system in the diabetes state. Methods: Eight-week-old db / db mice were randomized to candesartan 1 mg / kg, candesartan 10 mg / kg, manidipine 10 mg / kg, or placebo via gavage for 6 weeks.Their age-matched nondiabetic littermates db / m mice were treated with placebo and acted as nondia-betic controls. After 6 weeks’ treatment, an intraperitoneal glucose tolerance test, immunohistochemical staining of oxidative stress markers, insulin, CD31, azanstaining and an electron microscopy observation were performed. Results: Chroniccandesartan treatment provided an improvement of glucose tolerance, and greatlyrescued islet β-cell mass. Can desartan treatment also notably decrea sed staining intensity of oxidative stress markers, as well as attenuating intra-islet fibrosis and impacted blood supply in the islet. the electron microscopy observation, candesartan-treated animals exhibited improved granulation and less remarkable endoplasmic reticulum and golgi bodies; can, candesartan treatment greatlyrelieved the swelling of mitochondria to nearly normal. Both the benefits of reduc-ing oxidative stress and ultrastructure protection were in a dose-dependent and blood pressure-independent manner. Conlusion: After diabetes was initiated, candesartan treatment could not reverse the state of diabetes, but it effectively improved glucose tolerance and protected β-cell function by attenuating oxida-tive stress, islet fibrosis, sparsity of blood supply and ultrastructure disruption in dose-dependent and blood pressure-independent manner.