RESUMEN
Objective To investigate the effect of fenofibrate on glucolipid metabolism and insulin sensitivity in lipoprotein lipase heterozygous knockout ( LPL+/-) mice, and to explore its mechanism. Methods LPL+/- mice and wild type ( WT) C57 mice were selected and divided into 3 groups ( n=6 each group):LPL+/-( FB) group, LPL+/-(W)group,andWTgroup.MiceinLPL+/-(FB)groupweregavagedwithfenofibrate(50mg·kg-1·d-1)for8 weeks. Mice in LPL+/-( W) and WT groups were orally fed with the same volume water as that in LPL+/-( FB) group for 8 weeks. Body weight was observed. Plasma triglyceride ( TG ) and free fatty acid ( FFA ) were measured. Intraperitoneal glucose tolerance test in 3 groups of mice were performed. The glucose area under the curve ( AUCG) and homeostasis model assessment for insulin resistance index ( HOMA-IR) were calculated. Insulin-stimulated Ser473 Akt phosphorylation in liver and skeletal muscle was measured by Western blot. Reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined by dihydroethidium staining method and superoxide dismutase ( SOD) and catalase ( CAT) mRNA expression levels were detected by real-time PCR. Results Compared with LPL+/-( W) mice, body weight of LPL+/-( FB) mice was lowered, plasma TG and FFA levels were decreased by about 46.0％and 76.5％respectively, and fasting insulin level and HOMA-IR were decreased while there were no significant differences in fasting glucose level and AUCG between two groups. Insulin-stimulated Ser473 Akt phosphorylation levels in liver and skeletal muscle of LPL+/-mice were enhanced by fenofibrate. ROS level in skeletal muscle of LPL+/-( FB) mice was lower than that in LPL+/-( W) mice while there was no significant difference in ROS of liver between two groups. Fenofibrate significantly increased SOD and CAT mRNA expressions in skeletal muscle of LPL+/-mice, but not in liver. Conclusion Fenofibrate reduces body weight, ameliorates lipid metabolism, and improves insulin sensitivity in LPL+/- mice, with reduced oxidative stress.
RESUMEN
The localization and development of substance P (SP) like immunoreactive retinal neurons in the adult, newborn and postnatal New Zealand albino rabbits were studied with immuaocytochemistry ABC method. We found most of the SPlike immunoreactive somas in adult rabbit retina located in inner margin of inner nuclear layer (INL) and ganglion cell layer (GCL). Their processes ramified in the lamina 1,3 and 5 of inner plexiform layer (IPL). Some immunoreaetive fibers in the layer of optic nerve fiber (LON) were occasionally observed. The highest cell density of SP-like somas occured in the visual streak (VS). The cell density gradually decreased from the VS to the ventral and dorsal periphery. In the new born rabbit retina, the labelled cell bodies and their processes appeared. Most of them located in the GCL, and a few of them located in the' INL. Their processes formed discontinuous layer in the lamina 5 and never seen in the lamina 3. The cell density of SP positive somas gradually increased from newborn to postnatal 4 th day. From postnatal 6 th day to 12 th day, the cell density gradually decreased. From postnatal 12 th day the somas mainly located in the INL. On the 20th day after birth the distribution and morphology of SP-like immunoreactive somas and processes had approached that of mature age. These results suggest that rabbit retinal SP-like immunoreactive neurons had appeared at prenatal period and continuously developed after birth.