Impacts Of Overexpression Of CXCL16/SR-PSOX On Blood Lipids, Organizations And Related Inflammatory Factors In High Fat Diet Mice

Objective To screen the homozygous CXC chemokine ligand16（CXCL16）transgenic mice which could transmit the CXCL16/SR-PSOX target gene to the nextgenerations stably, and to observe impacts of overexpression of CXCL16/SR-PSOXon blood lipids, organizations and related inflammatory factors in high fat diet mice.Methods Heterozygous transgenic mice containing CXCL16/SR-PSOX wereselected for breeding and their offsprings were generated by inbreeding of the samelitters. Homozygous transgenic mice were confirmed by test cross.8week oldCXCL16（+/+）, CXCL16（+/-）from F11transgenic mice and C57BL/6J mice wereassigned at random to two groups. The control group was fed with standard diet, thehigh fat group was fed with15%fat,3%cholesterol,4%full cream milk powder,10%egg yolk and0.5%sodium cholate. After18weeks, all mice were killed andtheir weight, TG, TC, HDL-C, LDL-C, sCXCL16, MMP-9serum levels were assayed.Tissues of heart, aorta, liver, kidney were taken and HE-stained sections wereprepared for pathological analysis. Oil red o staining of aorta was observed under thedissection microscope to estimate the extent of atherosclerosis. Expression of MMP-9in tissue and aorta sinus lipid lesions was detected by immunohistochemical（IHC）.Results1.Homozygous male mouse F9-2-3and female mouse F8-1-2had beenconfirmed by inbreeding of the same litters and test cross, all their offsprings werepositive detected by PCR.2.After18weeks of high-fat and standard feeding, the weight and the TC, HDL-C LDL-C blood level in HFD group was higher than SD group. The weight, LDL-Clevel in CXCL16(+/+) was higher than in CXCL16(+/-)(P<0.05); the weight, TC,LDL-C level in CXCL16(+/+) was higher than in WT(P<0.05); and the LDL-C levelin CXCL16(+/-) was higher than in wild type(P<0.05). With TG stand at a low levelin all mice.3.In HFD group, there were significant fat deposition diseases in livers, kidneys andintestines in all transgenic mice, while diseases in CXCL16(+/+) mice were mostserious, changes in CXCL16(+/-) and WT were identical; meaningful lipid lesionshave been seen on aortic valves and perivalvular tissues in CXCL16trans and onlymodest lesions showed in WT. There were no obvious changes in either hearts orbrains in all mice.4.The sCXCL16blood level in CXCL16(+/+) mice was higher than in SDmice(P<0.05). There were no differences in MMP-9blood level between three groupsof SD. The blood level of both sCXCL16and MMP-9increased in HFD mice, whilelevels in CXCL16(+/+) were higher than in CXCL16(+/-) and WT(P<0.05).5.IHC of aortic valves and perivalvular tissues prompted a high level of MMP-9inaortic sinus lesions, especially in CXCL16(+/+).Conclusions1.We obtained homozygote transgene mouse stably expressedCXCL16/SR-PSOX.2.After18weeks of high-fat feeding, the non HDL-C blood level and expression ofMMP-9in CXCL16/SR-PSOX transgenic mice increased more significantly.Moreover, lipid deposition diseases in tissues of transgenic mice were more serious.Thus, overexpression of CXCL16/SR-PSOX could lead to more serious lipidmetabolism disorders.