The Effects And Mechanisms Of Chronic Intermittent Hypoxia On Atherosclerosis And Caveolin-1of Rat’s Offspring

Objective：Through the establishment of pregnant rats and offspring ofchronic intermittent hypoxia model to explore the impact of CIH onoffspring atherosclerotic lesions and its possible mechanism involved.Methods:16pregnant SD rats at7days pregnant were randomly divided intotwo groups, namely normoxia and CIH group. After delivery, two maleoffsprings of each mother rat were selected and fed to4weeks of age,then according to pregnant rats experienced CIH or not,they were randomlydivided into normoxia group and CIH group to become the following fourgroups: intrauterine normoxia+offspring normoxic group (control group),intrauterine normoxia+offspring CIH group, intrauterine CIH+offspringnormoxia group and intrauterine CIH+offspring CIH group（n=8），whileoffspring CIH group was experienced intermittent hypoxia for12weeksagain. Then the structure of thoracoabdominal aortic specimens wasexamined by pathology.The thickness of artery intima and media weremeasured. The protein expression of nuclear factor-κB p65(NF-κBp65),Caveolin-1, extracellular signal-regulated kinase1/2(ERK1/2) andphosphorylated extracellular signal-regulated kinase1/2(p-ERK1/2) ofoffspring arteries were measured by western-blot analysis.Results:(1) CIH can cause the arterial intimal of offspring ratsthickening: intrauterine CIH+progeny normoxic group (3.800±0.543μm),intrauterine CIH+progeny CIH group (6.440±0.977μm), intrauterinenormoxia+progeny CIHgroup (5.692±0.708μm) compared with the controlgroup (1.555±0.259μm), the difference was statistically significant(P<0.001)，while the difference of the medium was not statisticallysignificant (P=0.974).（2）CIH can cause NF-κBp65protein expression ofoffspring rats increase: intrauterine CIH+progeny normoxic group (0.020±0.002),intrauterine CIH+progeny CIH group(0.024±0.002), intrauterine normoxia+offspring CIH group(0.022±0.001) compared with the controlgroup(0.013±0.001),the difference was statistically significant(P<0.001).（3）CIH can cause Caveolin-1protein expression of offspringrats increase: intrauterine CIH+progeny normoxic group (0.348±0.027),intrauterine CIH+progeny CIH group (0.380±0.027), intrauterinenormoxia+offspring CIH group(0.361±0.037) compared with the controlgroup (0.230±0.014), the difference was statistically significant(P<0.01).（4）The differenece of the ERK1/2protein expression was notstatistically significant (P=0.998). CIH can cause p-ERK1/2proteinexpression of offspring rats decrease: intrauterine CIH+progeny normoxicgroup (1.530±0.272), intrauterineCIH+progeny CIH group (0.802±0.135),intrauterine normoxia+descendants CIH group (1.260±0.208) comparedwith the control group (2.303±0.176), the difference was statisticallysignificant (P<0.01).（5）All these influence caused by intrauterine CIHcould be aggravated significantly when offspring CIH is imposed.（6）NF-κBp65and Caveolin-1protein expression level was positivelycorrelated(r=0.848,P<0.001).Caveolin-1and p-ERK1/2protein expressionlevel was negatively correlated(r=0.-810,P<0.001).The proteinexpression level of NF-κBp65and thickness of artery intima waspositively correlated (r=0.880, P<0.001). The protein expression levelof Caveolin-1and thickness of artery intima was positively correlated(r=0.811, P<0.001).The protein expression level of p-ERL1/2and thicknessof artery intima was negatively correlated(r=-0.877,P<0.001).Conclusions:1、Intrauterine CIH can induce the offspring emergenceatherosclerosis early lesions.2、The offspring CIH can aggravate theseverity of atherosclerosis induced by intrauterine CIH, both have asynergistic effect.3、NF-κBp65/Caveolin-1/p-ERK1/2signaling pathwaymay be an important mechanism of CIH-induced atherosclerosis.