BACKGROUND: Diabetic cardiomyopathy, a serious complication of diabetes, is an important factor of increased mortality in patients with diabetes. Therefore, providing an effective experimental animal model is particularly important for studying the pathogenesis and treatment methods of diabetic cardiomyopathy. OBJECTIVE:To explore the method of establishing Wistar rat models of diabetic cardiomyopathy. METHODS:Forty rats were randomly divided into the control group (n=10) and diabetic cardiomyopathy group (n=30). The rats in the diabetic cardiomyopathy group were intraperitonealy injected with 60 mg/kg streptozotocin at a time to establish rat models of diabetic cardiomyopathy. The rats in the control group were given the same dosage of citric acid buffer by the same way. The rats in these two groups were al fed with non-fat high-sugar normal diet. RESULTS AND CONCLUSION:Compared with the control group, after 3 weeks of injection with streptozotocinin in rat models of diabetic cardiomyopathy, blood glucose level was significantly increased, myocardial cels arranged in disorder, the nuclei were of different sizes, colagen content in the myocardial tissue was significantly increased, and colagen fibers were thick and disordered. In addition, the mRNA and protein levels of transforming growth factorβ1 and type I colagen, two indices reflecting myocardial fibrosis, were markedly increased. These results indicate that intraperitonealy injecting large doses of streptozotocin (60 mg/kg) at a time and feeding with non-fat high-sugar normal diet could establish a stable rat model of type 1 diabetic cardiomyopathy. This method is safe and effective with high feasibility.

Aim To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide(DMTCCI) , an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. Methods HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition.Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit. Results DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0. 24 μmol · L-1. The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated,while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 μmol · L-1 of DMTCCI in HL-60 cells. Conclusion DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might playa role in the apoptosis process induced by DMTCCI.

OBJECTIVETo investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice.

METHODSEight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting.

RESULTSThe mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group.

CONCLUSIONSitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.

Animals ; Apolipoproteins E ; genetics ; Diet, High-Fat ; Dipeptidyl-Peptidase IV Inhibitors ; pharmacology ; Early Growth Response Protein 1 ; metabolism ; Fibronectins ; metabolism ; Gene Knockout Techniques ; Kidney ; metabolism ; Lipids ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Real-Time Polymerase Chain Reaction ; Sitagliptin Phosphate ; pharmacology

BACKGROUND: In the process of bone defect healing, the use of biological materials loaded with drugs for local defect intervention can accelerate the repair of the defect, which provides a new method for the local treatment of bone defects. OBJECTIVE: To introduce the local application of bone tissue engineering scaffolds loaded with bisphosphonates in bone defect repair and to summarize the effects of bone tissue engineering scaffolds as a drug delivery system on the bone defect healing. METHODS: The authors retrieved PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases with "bisphosphonates, alendronate, zoledronate, bone defect, bone tissue engineering" as key words for relevant articles published from 2006 to 2018. Initially, 235 articles were retrieved, and finally 70 articles were selected for further analysis. RESULTS AND CONCLUSION: Bisphosphonate drug is an effective inhibitor of osteoclast dissolution. It can form a drug sustained release system on the local defect by being loaded to composite scaffolds, promote the formation of new bone and accelerate the healing of the defect. For the drug delivery system of bisphosphonates, suitable scaffold materials are crucial to the osteogenic effect of composite scaffolds in the defect area. At present, the carrier materials used for bisphosphonate-loaded composite scaffolds are mainly divided into organic materials and inorganic materials. Most polymeric organic materials can directly load bisphosphonates to form good drug sustained release in the local area and obviously exert their pro-osteogenic effects, while natural materials and most inorganic materials are often combined with other materials to form composite materials as carriers to optimize the carrier performance. Most studies have also confirmed that these composite materials loaded with bisphosphonates in the defect area exert osteogenic effect in the defect area.

OBJECTIVE: To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism. METHODS: Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry. RESULTS: In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group ( < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner. CONCLUSIONS Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.