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Objective To investigate the protective effect and mechanism of MST1 inhibition on kidney tissue in diabetic rats,and to find a new therapeutic target for diabetic nephropathy.Methods Total of 54 male SD rats enrolled in this study were divided into 3 groups including normal control (group A,n=18),MST1 inhibition group (Group B,n=18) and diabetes group (group C,n=18).Diabetes was induced by a single streptozotocin (STZ,50 mg/kg) injection in group B and group C.rats in group B received lentiviral vector contain Mst1 interference RNA (shRNA) and the rats in group C received empty vector.The end of 4th,8th and 12th week after modeling were considered as time points in this study.At each time point,the level of 24 hours urine protein (24-HUP),blood glucose and serum creatinine were examined.Pathological changes were observed with HE stain; Injury of podocyte and glomerular basement membrane (GBM) were examined with transmission electron microscope (TEM).The intensity and location of MST1 in kidney tissue were detected by immunohistochemistry.The level of MST1,Phosphorylated-MST1,nephrin,Caspase-3 and FasL were detected by western bloting.Results (1) At the starting point,there were no significant differences among groups in terms of weight,activity,eating and drinking.Since the end of 72nd hour after modeling,the levels of glucose in both group B and group C,compared to those in group A,significantly increased (P ＜ 0.05).There was no significant difference between group B and group C for glucose level at each time point (P ＞ 0.05); the level of 24-HUP increased significantly since the end of 4th week after modeling,and the level in group C was higher than its counterpart in group B at the same point (P ＜ 0.05); (2) There was no significant pathological lesion observed in group A.Without obvious K-W nodular changes,mesangial proliferation was observed in group B and group C.It was shown by TEM that podocyte fusion and thickening of the GBM could be found in group B and group C.The pathological change in group B was better than that in group C; (3) Compared to group A,it was shown by western blot that the levels of MST1,Phosphorylated-MST1,Caspase-3 and FasL in group B and group C were significantly higher (P ＜ 0.05),and the levels of nephrin in group B and group C were significantly lower (P ＜ 0.05) since the end of 4th week after modeling.Meanwhile,the levels of MST1,Phosphorylated-MST1,Caspase-3 and FasL in group B were significantly lower than that in group C at each time point (P ＜ 0.05),the level of nephrin in group B was significantly higher than the one in group C; (4) It was shown by immunohistochemistry that there was low MST1 expression in normal condition,especially in cytoplasm of tubular epithelial cells.The level of MST1 in group B and group C significantly increased after modeling,and the change could be the same as Western blot shown.Conclusions MST1 pathway could be involved in kidney injury induced by diabetes.MST1 inhibition could alleviate the kidney injury in STZ-induced diabetes animal model.
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Objective To investigate the effect of echinococcus granulosus antigen B on the severity of streptozotocin induced diabetes mellitus.Methods Thirty male BALB/c mice were randomly divided into 3 groups:echinococcus granulosus antigen B group (group A,n =10),normal saline group (group B,n =10),control group (group C,n =10).Mouse in group A was injected by echinococcus granulosus antigen B and mouse in group B was given normal saline,Type 1 diabetes was induced.After 3 weeks,mice were executed and pancreases were scored on insulitis by HE staining.Serum IFN-γ and IL-4 levels were measured by ELISA.Results After 3 weeks of the establishment of diabetes model mouse body weight in group B and C decreased significantly compared with that in group A.Mouse mean blood glucose level in group A was significantly lower than that in group B and C.There were less than 40％ of islets with lymphocytic infiltration in group A,compared with 80％ in group B.The average Ridit was 0.423,0.519,and 0.561 in group A,B and C respectively,P ＜ 0.05.IL-4 level in group A was significantly higher than that in group B and group C [(71.6 ± 12.4) ng/ml,(12.6 ± 5.6) ng/ml,(14.2 ± 7.2) ng/ml,P ＜ 0.05].IFN-γ level in group B and group C were higher than that in group A [(276.1 ± 41.7) ng/ml,(352.2 ± 52.2) ng/ml,(358.1 ± 53.4) ng/ml,P ＜ 0.05].Conclusions Type 1 diabetes is organ specific T lymphocyte mediated autoimmune disease.Echinococcus granulosus antigen B has protective effects on diabetes mellitus in mice couteracting autoimmune injury to the islets by streptozotocin,probably by a mechanism related to immune deviation of Th1 to Th2.
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BackgroundResearch demonstrated that vitamin D3 mediated by its receptor has the potent nonclassical effects,including immunomodulatory,antiinflammatory,and neuroprotective properties,and it can enhance the secretion and sensitivity of insulin and therefore down-regulate hyperglycemia and attenuate the corneal edema.ObjectiveThe present study was to investigate the protective effect of vitamin D3on ocular structure in experimental diabetic rat.Methods Twenty-two healthy SPF C57BL/6 rats were randomly divided into vitamine D3 group (8 rabbits),diabetic control group ( 11 rabbits) and normal control group ( 3 rabbits).2％ streptozotocin ( STZ,175 mg/kg)was intraperitoneally injected to create the diabetic models in the rats of the vitamine D3 group and diabetic control group.Blood glucose was examined for 3 times in the third day after STZ injection,and the rats with the blood glucose concentration ＞16.7 mmol/L was identified as the successful diabetic models.After modeling,the rat tail blood was collected for the monitoring of blood glucose.Two weeks after modeling,vitamine D3 was intraperitoneally injected in each week for 5 times.The fundus was examined using direct ophtalmoscope,and the eyeballs were obtained under the excessive anesthesia for the measurement of thickness of the central cornea,retina and choroids by histopathological examination once a week for 7 weeks after administration of vitamin D3.The administration of the animals complied with the Statement of ARVO.ResultsThe corneal edema appeared with the corneal thickness of (339.14± 11.13) μm in the first week and gradually attenuated with time elapse after modeling in the diabetic group ( F =382.446,P =0.000).The corneal thickness values were significantly decreased from the second week through the seventh week in the vitamin D3 group compared with diabetic control group(P＜0.05).The atrophy of the corneal epithelium was found from the fifth week to the seventh week in diabetic control group,but that in vitamin D3 group was slight (P＜0.05).The gradually thinning of the choroids was seen from the first week to the seventh week in the diabetic control group ( F =437.411,P =0.000 ),however,the thickness values in the vitamin D3 group were significantly increased in comparison with the diabetic control group in various time points (P＜0.05).The retina thickness was gradually reduced during the seven-week duration in the diabetic control group (F =91.859,P =0.000),but no significant change was identified in retina thickness in the vitamin D3 group(P＞0.05).ConclusionsVitamin D3 has prevent and therapeutic effects on experimental diabetic oculopathy.
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It is widely described in the literature that diabetic patients present hearing impairment. Despite the histological alterations of the internal ear structures in these patients as well as in experimental models of diabetes, to the best of our knowledge, an histological evaluation of the vestibulocochlear nerve have not been performed. In the present study, ultrastructural alterations are described and compared between a spinal nerves and a cranial nerve in rats with chronic induced diabetes. Male Wistar rats (n = 12), fed with standard diet from the animal care facility at 42 days of age were used. Induced diabetic animals (n=6) were fasted for 12 hours prior to being injected intraperitoneally with streptozotocin (STZ - 60mg/kg) in a single dose. Control animals (n=6) received (0.01 mol/l citrate buffer, pH 4.5) vehicle alone. Ten weeks after STZ injection the animals were perfused intracardially with Karnovsky solution. Right and left vestibulocochlear nerves were dissected and histologically processed for epoxy resin embedding. Samples were imaged with the transmission electron microscope. Large myelinated fibers with morphological signs of axonal atrophy in the vestibulocochlear nerves were readily observed. These results suggest that chronic STZ-induced diabetes in rats caused alterations in the myelinated fibers and Schwann cells, compatible to the classic diabetes signs and symptoms. Morphological alterations of the vestibulocochlear nerve in diabetes is described for the first time and contributes information for a better understanding of why there are changes in hearing observed in diabetic patients.
Se ha descrito ampliamente en la literatura que los pacientes diabéticos presentan discapacidad auditiva. En estos pacientes, a pesar de las alteraciones histológicas de las estructuras del oído interno, así como en modelos experimentales de diabetes, que mejoran nuestro conocimiento, la evaluación histológica del nervio vestibulococlear no ha sido realizada. Se describen y comparan las alteraciones ultraestructurales entre un nervio espinal y uno craneal en ratas con diabetes crónica inducida. Fueron utilizadas 12 ratas Wistar machos, de 42 días de edad, alimentadas con dieta estándar. Los animales diabéticos inducidos (n = 6) se mantuvieron en ayuno por 12 horas antes de ser inyectados por vía intraperitoneal con estreptozotocina (STZ - 60mg/kg) en una sola dosis. Los animales control (n = 6) sólo recibieron inyección de 0.01 mol/l buffer, citrato pH 4,5. Diez semanas después de la inyección de STZ, los animales fueron perfundidos intracardiacamente con solución de Karnovsky. Los nervios vestibulococlear derecho e izquierdo fueron disecados y procesados histológicamente para ser incluidos en resina epoxy. Las muestras fueron estudiadas con microscopio electrónico de transmisión. Fueron observadas fácilmente, grandes fibras mielinizadas con signos morfológicos de atrofia axonal en los nervios vestibulococlear. Estos resultados sugieren que la diabetes crónica inducida por STZ en ratas causó alteraciones en las fibras mielínicas y células del neurilema, compatible, con los signos y síntomas clásicos de la diabetes. Alteraciones morfológicas del nervio vestibulococlear en la diabetes son descritas por primera vez, lo que aporta información para una mejor comprensión de por qué hay cambios en la audición en los pacientes diabéticos.
Subject(s)
Animals , Male , Adult , Diabetes Mellitus, Experimental/chemically induced , Vestibulocochlear Nerve , Vestibulocochlear Nerve/ultrastructure , Microscopy, Electron/methods , Cochlear Nerve/physiopathology , Rats, Wistar/physiologyABSTRACT
Some kinetic characteristics of beta-adrenoceptor on circulating intact lymphocytes (CIL) in the combined renovasoeular hypertensive and diabetic (HD) rats were studied and the relation of betareceptos between CIL and cardium as well as the morphologic changes in the processe of dilated cardiomypathy (DCM) were observed. The results show that: the density of beta-adrenoceptor on CIL (Bmax) was going up 41.28%(P0.05), but the Kd was still 50.01%(P
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Changes of liver enzyme histochemistry and characteristics of glucagon receptor on liver cell plasma membrane were observed in streptozotocin-induced diabetic rats. The results showed that glycogenolytic and glyconeogenetic enzyme activities of liver were increased in diabetic rats and were higher than those of normal rats. There were no marked differences concerning both low and high affinities of glucagon receptors between normal and diabetic rats, but the concentration of low affinity glucagon receptor was significantly higher for diabetic rats than for normal rats. Compared with untreated diabetic rats, the concentration of high affinity glucagon receptor was normalized and that of low affinity receptor decreased by 30. 6% in insulin-treated diabetic rats. The present study implies that: 1)DURING insulin deficiency the increase in liver glyconeogenesis may be one of the important factors to induce increment of liver glucose output; 2) the increase in glucagon receptor binding to liver in streptozotocin-induced diabetic rats may provide a cellular basis for the increased glycemic and ketonemic response to glucagon in insulin-deprived diabetics; 3) since in diabetic rats insulin treatment results in a reversal of increased glucagon binding, it is possible that insulin regulates the glucagon receptor either directly or through its effect on the plasma glucagon concentration.
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In this study, the effect of hespridin, a natural flavonoid, on renal function and morphology in streptozotocin induced diabetic rats was evaluated. The result was compared with that of aminoguanidine which can inhibit the formation of advanced glycosylation end products (AGEs) and can decreased diabetic complications in experimental diabetes. The results showed that excretion of urinary protein, and the content of AGEs and LPO decreased, while the mesangial expansion and basement membrane thickening were retarded in diabetic rats treated with hespridin. These indicate that hespridin plays the same protective role as aminoguanidine in inhibiting formation of AGEs, thus preventing the development of nephropathy in STZ induced diabetic rats.