The Experimental Investigation Of The Relationship Between Hyperlipidemia And Endothelial Cell In Rats

Background: Atherosclerosis is a multifactorial disease process initiated by a variety of pathogenetic mechanisms. Initiation and progression of the atherosclerotic plaque involve complex pattems of interaction between the cells of the arterial wall. In which hypercholesterolemia is the crucial factor and endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. Recent studies show that reactive oxygen species(ROS) play an important part in vascular dieases especially in atherosclerosis. Probucol is the most antioxidant in the world now, it can relieve from ROS to lesion blood vessel endothelium, and delay the procession of atherosclerosis. Based on the establishing atherosclerotic mode of rats, we use different measures to observe the response of endothelial function to hyperlipidemia and atherosclerosis, and the mechanism of the procession of atherosclerosis.Methods: forty-eight adult male SD rats were randomly divided into 6 groups, each contained 8 rats: the control rats, L-NAME fed rats, high fat diet rats, high fat diet+VitD₃(ip) rats, high fat diet + Probucol rats, high fat diet + VitD₃(ip)+Probucol rats. Weight and systolic pressure(by tail cuff method) were tested every four weeks. In the end, rats were infused with 1% acetylcholine and 1% sodium nitroprusside respectively for 6 minutes through a jugular vein catheter. Systolic pressure was recorded through a carotid artery catheter simultaneously. After recording the time course of the change in systolic pressure, samples of blood were collected rapidly from heart for the tests of TG, TC, HDL-C, LDL-C, Glu, Ins, NO, NOS, SOD, T-AOC, MDA, O₂^- activity. And calculate the HOMA-IR. Then we make arteriae aortas into pathological sections in order to make them HE dyed and MMP-9 immunohistochemistry staining.Results:1. The body weight was significantly decreased in the rats of groups high fat diet(P＜0.01). Systolic pressure(by tail cuff method) was significantly increased in the rats of groups L-NAME and high fat diet(P＜0.01).2. At the end of study, the descending blood pressure extent after infusing sodium nitroprusside was significantly higher than acetylcholine in L-NAME fed rats(P＜0.01), all the high fat diet rats compared with the control were nonsignificantly changed(P＞0.05).3. The plasma TG, TC, HDL-C, LDL-C level were found to be significantly elevated in the rats of groups high fat diet(P＜0.01). Plasma TG level in probucol intervened rats were not significantly changed(P＞0.05). The serum levels of Ca²⁺ were markedly increased in the rats of groups which were treated VitD₃.4. Serum NO, NOS, T-AOC level in L-NAME fed rats were significantly decreased(P＜0.01), MDA, O₂^- level were significantly elevated(P＜0.01), SOD level had no significantly changed(P＞0.05). In High fat diet rats groups, the plasma NO, NOS, MDA, Glu, Ins, HOMA-IR level were significantly elevated(P＜0.01), T-AOC level were found to be significantly decreased(P＜0.01), SOD level was not found to be significantly changed(P＞0.05). In probucol intervened rats, the plasma MDA level were significantly decreased(P＜0.01), NO, NOS, T-AOC level were significantly elevated(P＜0.01), O₂^-, SOD, Glu, Ins, HOMA-IR level had no significantly changed(P＞0.05).5. MMP-9 immunohistochemistry staining showed that MMP-9 were gatherer in the atherosclerosis plaque. But MOD expression were not significantly different between groups(P＞0.05), IOD expression were found to be significantly elevated in the rats of groups high fat diet(P＜0.05). IOD expression were found to be significantly decreased in probucol intervened rats(P＜0.05). These findings showed that Probucol can decrease inflammation mediator expression.Conclusions:1. These findings demonstrate that L-NAME fed can induce endothelium dysfunction and result in hypertension ultimately.2. Insulin resistance induced by high fat diet is the cause of hypertension. Oxidative stress induced by high fat diet has more relationship with AS in this test, which the blood dynamic has no changed in high fat diet rats maybe: the duration of the experiment was too short(only 12 weeks) or the different between species(the natural antioxidate of SD rats), which has no effect the EC/NOS/NO signal transport system.3. Probucol can reduce inflammation mediator expression by the effective of antioxidate, so it may delay the process of atherosclerosis.4. The Propylthiouracil caused the low weight due to hypothyroidism.