ABSTRACT
Objective To investigate the regulating effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on Bcl-2, Bax and Caspase-8 in hippocampus neuron damage in diabetes mellitus with depression (DD). Methods Hippocampal neurons from 18 d pregnant rats were primitively cultivated, and then combination of glucose and corticosterone was used to construct DD simulation environment. Cultivated hippocampal neurons were randomly divided into normal group, blank serum group, model group, positive medicine (metformin+fluoxetine) serum group and to-be-tested medicine (ZJJF) serum group. Normal group and model group were given same amount culture medium, while other group were given relevant amont of 10％ medicine serum or blank serum. After modeling intervention for 18 h,Hoechst staining was used to detect the apoptosis of hippocampal neurons. The expression of Bcl-2, Bax and Caspase-8 was detected by high content analysis. Results Compared with the control group, hippocampal neuron dendrites ruptured or decreased, neural network connection decreased, cells showed significant staining, broken, uneven distribution of light spots, the expression of Bcl-2 protein decreased significantly (P<0.05), but Bax and Caspase-8 were increased (P<0.05, P<0.01). Compared with the model group, hippocampal neurons in both positive medicine serum group and ZJJF serum group gradually recovered. Hoechst staining showed that the nuclei were significantly homogenized, local highlights were significantly reduced, Bcl-2 protein expression levels were significantly increased (P<0.05, P<0.01), while Bax and Caspase-8 were obviously down-regulated (P<0.05, P<0.01). Conclusion ZJJF has protective effects on hippocampal neurons in DD of model rats, and its mechanism is related to regulating the expression of Bcl-2, Bax and Caspase-8 in hippocampus neuron.
ABSTRACT
Objective To observe the effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on the ability of learning and memory and the expressions of JNK, Bcl-2 and Bax in hippocampus in diabetic rats with depression; To explore the protective mechanism of hippocampal damage in diabetic rats with depression. Methods High-fat gavage combined with intravenous injection of STZ was used to establish the model of diabetic rats. 28 days of chronic stress was given continuously and diabetic rats complicated with depression were built successfully. Then rats were randomly divided into 6 groups, including normal, model, positive medicine, high-, medium-, and low-dose of ZJJF groups. After the last administration, Morris water maze was used to detect escape latency time;Western blot was used to disclose the protein expressions of JNK, Bcl-2 and Bax in rat hippocampaus;RT-PCR was used to test the gene expressions of JNK and Bcl-2 and Bax. Results Compared with the normal group, escape latency time in model rats was significant longer (P<0.01), the protein and gene expression of JNK and Bax in rat hippocampaus significantly increased, Bcl-2 was markedly decreased (P<0.05, P<0.01);Compared with the model group, escape latency time in positive medicine group and high-dose of ZJJF group was significant shorter (P<0.01), the protein and gene expressions of JNK and Bax significantly decreased, and Bcl-2 markedly increased (P<0.05, P<0.01). Conclusion ZJJF can significantly improve the ability of learning and memory in diabetic rats with depression, which might be associated with preventing neuronal apoptosis in hippocampus.
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Objective To study the pathologic pattern and clinical feature of type 2 diabetes mellitus complicated with chronic kidney diseases (CKD). Methods Clinicopathological features of 155 type 2 diabetic patients complicated with CKD were collected and analyzed retrospectively. The patients were divided into four groups: typical diabetic glomerulopathy (DG),atypical diabetes-related renal disease (ADRD), non-diabetic renal diseases (NDRD) and DG complicated with NDRD. Results Renal biopsies revealed DG accounted for 18.7% of the patients, ADRD accounted for 12.9%, NDRD accounted for 60.0%, and DG complicated with NDRD accounted for 8.4%. In DG group, duration of type 2 diabetes was longer;the level of fast blood glucose, systolic blood pressure, mean arterial pressure and prevalence of diabetic retinopathy (DR) were higher;proteinuria was heavier and evaluated glomerular filtration rate (eGFR) was lower. In ADRD group, body mass index and prevalence of obesity were higher;dyslipidemia was more severe. Gross hematuria and acute renal insufficiency could be only found in NDRD group.Without DR, duration of diabetes under 5 years, gross hematuria, acute renal insufficiency,evidences of autoimmune diseases and proteinuria≥3.5 g/24 h but eGFR ≥60 ml/min were specific valuable predictors for NDRD. Conclusions Renal injuries in type 2 diabetic patients are structural heterogeneous, in which NDRD is more common and is different from ADRD and DG.Renal biopsy should be considered when type 2 diabetic patients complicated with CKD present at least one characteristic as follows: duration of diabetes under 5 years, without DR, history of gross hematuria, acute decrease of renal function, evidences of autoimmune diseases and proteinuria ≥ 3.5 g/24 h but eGFR ≥ 60 ml/min.
ABSTRACT
Objective To find out a more rational pathological classification criteria for renal injury in patients with type 2 diabetes mellitus. Methods The renal clinicopathological features of forty-nine type 2 diabetic patients with maeroalbuminuria were collected and were compared retrospectively. The patients without diabetic renal disease were excluded. According to the pathological features, the patients were divided into two groups: typical diabetic glomerulopathy (DG) and atypical diabetes-related renal disease (ADRD). Results The renal biopsy revealed DG accounted for 59.2% of the patients, while the remaining 40.8% presented atypical renal injury defined as ADRD. In DG group, volume fraction of mesangium per glomerulus, glomerular basement membrane width, atrophic tubules index, intersititium injury index and prevalence of hyalinization of renal arteriole were higher; podocyte density per glomerulus was lower; duration of type 2 diabetes was longer; the level of fast blood glucose, systolic blood pressure, mean arterial pressure, proteinuria and prevalence of diabetic retinopathy (DR) were higher; glomerular filtration rate (GFR) was lower. In ADRD group, body mass index and prevalence of obesity were higher; dyslipidemia was more severe. GFR was negatively correlated with glomerular global sclerosis rate in both DG and ADRD group. Proteinuria was positively correlated with volume fraction of mesangium per glomerulus in DG. No correlation between proteinuria and pathological features was found in ADRD. DR (94.8%) and duration of type 2 diabetes over five years (90.7%) had high negative predictive value for DG. Conclusions Renal injuries in type 2 diabetes patients are heterogeneous. ADRD is an atypical renal injury in type 2 diabetes patients whieh is different from DG. DR and duration of diabetes are more helpful in predicting DG separating from ADRD.