ABSTRACT
Objective To study the effects of constant and intermittent high glucose on the apoptosis of cultured bovine retinal capillary pericytes (BRPs), and to investigate the role of mitochondrial apoptotic pathway in the apoptosis of BRPs. Methods After being cultured under glucose with different concentrations tot 6 days, the change of uhrastructure of BRPs was observed under electronmieroscope, the apoptosis of pericytes was detected by TUNEL method, the mitochondrial inner transmembrane potential (△Ψm) was detected by laser scanning confocal microscopy, the change of cytochrome c (cyt-c) was assayed by spectrophotometer and the expression of apoptotic genes was detected by immunohistochemical method and RT-PCR. Results (1) BRPs showed typical changes of apoptosis in constant and intermittent high glucose concentrations. The apoptosis induced by constant high glucose concentration was more obvious than that by intermittent high glucose. (2) Constant and intermittent high glucose concentrations obviously decreased △Ψm compared with control group. The △Ψm of BRPs was correlated negatively with the apoptotie rate of BRPs (r = - 0.89, P < 0.01) ; (3) Constant and intermittent high glucose concentrations increased the release of cyt-c from mitochondria to cytoplasm, and the concentration of cyt-c in the cytoplasm was correlated positively with the apoptotic rate of BRPs (P < 0.01) ; (4) Constant and intermittent high glucose concentrations increased the expression of proapoptotie gene Bax and decreased the expression of prosurvival gene Bcl-2, resulting in increased Bax/Bcl-2 ratio. Bax/Bcl-2 ratio was negative correlatied with the △Ψm of BRPs, and positively eorrclaticd with the concentration of cyt-c in cytoplasm and apoptotic rate (both P < 0.01).Conclusion Constant and intermittent high glucose concentrations could decrease △Ψm, increase the release of cyt-c and induce the apoptosis of BRPs, the effects being stronger with constant high glucose concentration. The mitochondrial apoptotic pathway plays an important role in the apoptosis of BRPs, in which Bax and Bcl-2 are involved.
ABSTRACT
@#ObjectiveTo investigate the role of serine/threonine kinase (Akt) and lipoprotein lipase (Lpl) in formation of nonalcoholic steatohepatitis (NASH) in rat with a fat-rich diet.Methods40 male Wistar rats were randomly divided into the 8-week-rich-fat group (n=10), 8-week-common-diet control group (n=10), 12-week-rich-fat group (n=10) and 12-week-common-diet control group (n=10). The lipid, cholesterol, glucose and insulin were examined, insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated, the expression of Akt and Lpl were detected with immunohistochemical method and morphological changes of liver were observed by transmission electron microscope (TEM).ResultsNASH was formed in each rat of 8-week-rich-fat group with characteristics of individual obese, increased liver volume, full and clear contour, gray-yellowish luster, greasy section and crisp quality. And it was accompanied by high lipoidemia (HL), liver fat cell denaturation, inflammatory cell infiltration in liver lobuler and cell death in liver. The expression of Akt was obviously reduced and the expression of Lpl was obviously weakened in liver. Lipid, cholesterol, glucose and insulin and IRI were gradually advancing. ISI was reducing and the insulin resistance formed. The data of fat-rich diet groups was significantly different with that of common-diet control groups (P<0.0001).Conclusion Steatohepatitis and insulin resistance can form in rat by feeding with rich-fat diet for 8 weeks. It causes the insulin and Lpl activeness reducing, and steatolysis barrier.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the potential role of insulin-like growth factor-1 receptor mRNA (IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.</p><p><b>METHODS</b>A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.</p><p><b>RESULTS</b>Weak expression of IGF-IR mRNA (5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P < 0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.</p><p><b>CONCLUSION</b>Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.</p>