ABSTRACT
Objective:To investigate the effects of Purendan Superfine Powder (PRD) on the retinal hemodynamics and the expressions of cytokines in the diabetic rats, and to elucidate its protective effect on diabetic retinopathy (DR) .Methods:Thirty-six male SD rats were randomly divided into control group, diabetes group, and PRD group (n=12) .The diabetes rat models were established by intraperitoneal injecting streptozotocin (STZ) in diabetes group and PRD group.After successful modeling, the diabetic rats in PRD group were given PRD (1.8g·kg-1) by gavage for 3months.The hemodynamics parameters of central retinal artery (CRA) of the rats were measured with color Doppler ultrasound.The expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA in retina tissue were detected by reverse transcription polymerase chain reaction (RT-PCR) .Immunohistochemical staining and Western blotting methods were used to detect the expression levels of VEGF and bFGF proteins in retina tissue of the rats.Results:Compared with control group, the blood glucose, urine volume, liver index and kidney index of the rats in diabetes group were significantly increased (P＜0.05) , the peak systolic velocity (PSV) , end diastolic velocity (EDV) and mean velocity (MV) of CRA were significantly decreased (P＜0.05) , the resistant index (RI) and pulsatility index (PI) of CRA were significantly increased (P＜0.05) , and the expression levels of VEGF and bFGF mRNA and protein in retina tissue were significantly increased (P＜0.05) .Compared with diabetes group, the blood glucose, urine volume, liver index and kidney index of the rats in PRD group were significantly decreased (P＜0.05) , the PSV, EDV and MV of CRA were increased (P＜0.05) , the RI and PI of CRA were decreased (P＜0.05) , the expression levels of VEGF and bFGF mRNA and protein in retina tissue were significantly reduced (P＜0.05) .Conclusion:PRD can protect the diabetic retinal microvascular injury by reducing the blood glucose level, increasing the blood supply of retinal tissue, increasing the amount of microcirculation blood perfusion, reducing the vascular bed perfusion resistance, and reducing the expression of VEGF and bFGF.
ABSTRACT
Objective:To investigate the influence of endoplasmic reticulum stress (ERS) in the degeneration of cochlear hair cells in the type 2diabetic mice, and to clarify its mechanism.Methods:Twenty clean Kun Ming male mice aged one month were selected and randomly divided into control group and model group (n=10) .The mice in model group were injected with STZ (40 mg·kg-1) to establish the type 2diabetic models.The fasting blood glucose levels of the mice were measured through collecting the vena caudalis blood of the mice.Auditory brain stem response (ABR) was used to detect the ABR threshold of the mice.Otoacoustic emission (OAE) test was used to detect the OAE threshold of mice.The defect rate of mouse cochlear outer hair cells was calculated by the mouse cochlear spreading technique.The expression levels of GRP78, caspase-12, p-ERK and Nrf2proteins were detected by Western blotting method.Results:Compared with control group, the fasting blood glucose levels of the mice in model group at the 7th and the 14th days had no significant differences (P＞0.05) , but the levels were increased significantly at the 21th, 28th and 35th days and the level reached the highest value at the 35th day.The ABR thresholds of the mice in model group at 8, 12, and 24kHZ were increased significantly compared with control group (P＜0.05) .Under the stimulation of low frequency, there was no significant change in the OAE threshold of the mice in model grouop compared with control group.The OAE thresholds of the mice in model group were increased significantly under the medium frequency and high frequency stimulation compared with control group (P＜0.05) .The defects of the cochlear hair cells were mainly concentrated on the bottom of gyrus of the mice, and the defects in middle temporal gyrus and parietal gyrus were less.Compared with control group, the defect rate in the bottom of gyrus of the mice in model group was increased significantly (P＜0.05) ;the defect rates in the middle temporal gyrus and parietal gyrus were increased, but there was no significant difference (P＞0.05) .The expression levels of p-ERK and Nrf2in the cochlear hair cells of the mice in model group were lower than those in control group (P＜0.05) , and the expression levels of GRP78and caspase-12were higher than those in control group (P＜0.05) .Conclusion:ERS can result in the increase of defect rate of cochlear outer hair cells and ABR brainstem hearing threshold of the diabetic mice and decrease the expression levels of p-ERK and Nrf2proteins, suggesting that ERS can promote the degenerative lesions of cochlear hair cells in the type 2diabetic mice.
ABSTRACT
Objective:To observe the inhibitory effect of metformin on the inflammatory response of Kupffer cells (KCs) of liver in the diabetic mice, and to explore its improvement on the phagocytic function of KCs, and to elucidate the protective mechanism of metformin on the KCs in the diabetic mice.Methods:The C57BLKS/J db/db mice were divided into diabetes group and diabetes+metformin group, and the C57BLKS/J db/m mice were divided into non-diabetes group and non-diabetes+metformin group, 8mice in each group.The KCs were cultured in vitro and the changes of ultrastrustures of KCs were observed by transmission electron microscope.The levels of interleukin 6 (IL-6) , tumor necrosis factorα (TNF-α) andγ-interferon (INF-γ) in the KCs were detected by ELISA.The expression levels of intercellular adhesion molecule 1 (ICAM-1) protein in the KCs was detected by Western blotting method.Transwell chamber assay was used to detect the neutrophil chemotaxis ability of the KCs, and the phagocytic ability of KCs was observed under inverted microscope.Results:The number of mitochondria and rough endoplasmic reticulum (RER) in the KCs of the diabetic mice was reduced, the RER expanded, the mitochondria swelled, and the lipid droplets were increased.Compared with non-diabetes group, the levels of IL-6, TNF-α, INF-γand the expression level of ICAM-1in the KCs of the mice in diabetes group were significantly increased (P＜0.05) ;the neutrophil chemotaxis ability of the KCs was enhanced (P＜0.05) , and the phagocytic ability was decreased (P＜0.05) .Compared with diabetes group, the levels of IL-6, TNF-α, INF-γand the expression level of ICAM-1in the KCs in diabetes+metformin group were significantly decreased (P＜0.05) ;the neutrophil chemotaxis ability was decreased (P＜0.05) , and the phagocytic ability was enhanced (P＜0.05) .Conclusion:Metformin can inhibit the inflammatory response of KCs in the diabetic mice and improve its phagocytic function and protect the KCs.