[The Preliminary Investigation of GLP-1 Receptor Agonist on Liver Steatosis in Obese Mice].

OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 µg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0.01 µg/ (g·d) , high-fat-diet], saline group (NS group, intraperitoneal injection of saline, high-fat-diet) , diet control group (D group, shifted to chow diet) and high-fat control group (M group, high-fat-diet) for 4-week treatments , respectively. The body mass and serum biochemical indicators of were detected. Liver tissues were stained with HE, and steatosis score was measured. RESULTS: After 4-week treatments, H group showed more body mass loss than L group and D group ( P<0.05). The serum alanine aminotransferase (ALT) level of NG group was higher than that of H, L, M, and NS groups ( P<0.05). Serum cholesterol and triglyceride declined to normal levels by diet intervention or drug treatment. High-dose exenatide treatment ran a risk of increasing serum uric acid level. The serum levels of aspartate aminotransferase (AST), glucose, homeostasis model assessment-insulin resistance (HOMA-IR), lipase, and amylase had no significant differences between groups (P>0.05). Hepatic steatosis score was reduced by diet intervention or drug treatment. CONCLUSIONS: High-dose exenatide treatment can effectively reduce body mass of obese mice, but it has little difference when compared with dietary intervention in improving blood fat and liver steatosis.

[MnSOD gene regulated by aminopeptidase N promoter specifically protects bone marrow from radiation].

BACKGROUND & OBJECTIVE: It is an effective way to induce radio-tolerant gene into hematopoietic cells in bone marrow for overcoming the suppression of radiotherapy on hematopoietic system. However, this also increases the radiation tolerance of tumor cells. This study was designed to investigate a method to specifically protect bone marrow cell from being damaged by radiation, along without increasing resistance of tumor cell to radiation. METHODS: The retrovirus vector of manganese superoxide dismutase (MnSOD) gene regulated by aminopeptidase N (APN) bone marrow-specific gene promoter was constructed and induced into myeloblastic KG1a and cancer cell BEL7402. MnSOD mRNA level was analyzed by PT-PCR; MnSOD activity in the cells was determined; the sensitivity of bone marrow cell and hepatic carcinoma cell to x-ray was detected by cell survival test; the cell apoptosis was analyzed with flow cytometry and fractural DNA electrophoresis. RESULTS: The MnSOD mRNA level and enzyme activity in KG1a cells transferred with the gene was obviously increased. Expression of MnSOD mRNA drove by APN myelo-specific promoter effectively inhibited apoptosis of KG1a cells induced by radiation and endowed KG1a cell line with the enhancement of tolerance to radiation, which increased by 3.7 folds compared to parental cells at the dose of 10 Gy. In contrast, the level of MnSOD mRNA, the enyme activity of MnSOD and the radiosensitivity had no significant change in BEL 7402 cells transduced with MnSOD gene. CONCLUSION: APN bone marrow-specific promoter could control MnSOD gene expression highly in myeloid cell and lower in cancer cell. In the process of killing of cancer cell by x-ray, MnSOD gene regulated by APN bone marrow-specific promoter could specifically protect myeloid cell. This study provides a new clue to solve the bone marrow suppression in high dose radiotherapy.