| Background and ObjectAortic Dissection is one of the most critical diseases in cardiovascular surgery. Itcharacterized by its onset nasty, fast progress and poor prognosis. The incidence of aorticdissection is increasing year by year. It has become one of the most serious diseases threatto human health. According to latest Clinical data, the incidence of aortic dissection is about5-30/100w,21%of suffers died outside hospitals,68.2%of patients die within48h after and90%patient die in1w. The main reason of dying attribute to the tear of aorta. Consideringthe treatment plan, the treatment for aortic dissection is still very limited, mainly includingendovascular stent implantation surgery and open heart surgery, the former operation willtake a long time, operation procedure is difficult and it will bring huge trauma to the patientsand the prognosis is poor; the latter one ask for strict indication and there is a recurrence.Therefore, we urgently need deeper understanding from the aspects of the pathogenesis ofaortic dissection for analysis and research, so as to explore new means of prevention andtreatment to prevent disease, alleviate pain, improves the prognosis of patients.The middle of aorta is mainly composed of collagen fibers, elastic fibers and vascularsmooth muscle cells. The link of collagen and elastic fibers play an important part ofmaintaining vascular tension. Vascular smooth muscle cell has an important role on theadjustment of the nutrient blood vessel walls, aortic VSMC of traumatic stress and so on forthe regulation of immune response has an important role. Aortic VSMC have twophenotypes, each of them have different biological characteristics. Contractile VSMC havea poor ability of proliferation and migration, the main function of contractile VSMC is tomaintain vascular contraction and relaxation; the synthetic VSMC have a strong ability ofproliferation and migration, mainly involved in the reconstruction of the extracellular matrix,maintaining the function of blood vessel function. Under some sudden situation, such asimpact of high speed blood flow, certain drugs and even injury blow case, these twophenotypes can mutual transformation. Current research shows that synthetic VSMC in thewall of aortic dissection organization increased obviously when comparing with the normalblood vessels tissue. Hence, most experts agree that due to the phenotype switch of VSMC,the aortic wall become less elasticity and toughness and more fragile. When confrontingwith a high speed blood flow, external factors such as trauma, blood vessel walls appearcrevasse, blood rushed to break eventually lead to the happening of the dissection.Cell autophagy is a kind of cell procedure. It is involved in self adjusting, self– protection. The main mechanism of autophagy is when confronting a specific environment,such as lack of energy, trauma and oxygen free radical, it will activate some intracellularproteins and cellular pathways, and induce autophagosome formation and mature gradually.Finally due to the formation of autophagy, the damaged proteins and organelles and foreignorganizations will be phagocytosis and digested, and then provide energy for cells, maintainhomeostasis for cell. In recent years, many studies have shown that autophagy is involvedin a variety of diseases such as tumor, diseases of the nervous system, arteriosclerosis,ischemia-reperfusion injury. In terms of cardiovascular disease, scientists have found inaortic aneurysm, pulmonary hypertension, coronary heart disease (CHD) in patients withvascular tissues, VSMC autophagy reaction also be stimulated. Autophagy has become oneof the hotspots in scientific research in the medical community.AngiotensinⅡ is one of the most important effect-protein in RAS, it is transformedfrom Angiotensin I under the treatment of ACE. It will show a power effect on vascular,brain, heart and kidney through AT1receptor. AngⅡ has involved in many pathologicalprocess, such as myocardial hypertrophy, heart failure and so on. According to the latestrearch, AngⅡ show a special role in the initial and progress of autophagy.In conclusion, we conceived that autophagy may be the reason of VSMC phenotypicswitching, which from dissecting aorta. When VSMC suffers severe extracellularenvironment disorder, excessive autophagy is induced at the internal of VSMC and result inVSMC phenotype switching, even apoptosis. Finally the function of the aortic wall isimpaired. At present, there is no animal experiments prove that the occurrence of aorticdissection involved with VSMC autophagy. So we build the mice model of acute aorticdissection, and detect the expression of autophagy-related protein in the tissue of aorta fromthe model. Our destination is providing provide foundation and basis for the furtherexploration of the role of autophagy on the pathogenesis of acute aortic dissection,We’d like to discuss those problems in the follow text.Part1The establishment of Aortic Dissection ModelObject Based on previous research results, we will establish a stable and efficient aorticdissection modelMethod45aging at3w FVB mice will be divided into β-amino acrylic nitrile combineangiotensin-Ⅱ groups, single β-amino acrylic nitrile intervention group and control group according to the random distribution method, each group consist with15mice. Then thecombining group will be given BAPN orally for4w and then angiotensin-Ⅱ subcutaneousfor48h and the single-BAPN group will be given BAPN orally for4w and control groupjust with normal feeding. During the intervention, per litter as a unit, will be weighted forevery5days, the amount of drinking water will be record every day. According to the weightof mice and the amount of water, the drug dose should be adjusted dynamic. After theintervention, by the method of spinal cord was put to death in mice, HE and VB stain willbe performed to detect the incidence of aortic dissection.Outcome The incidence of aortic dissection in the BAPN-AngⅡcombined group was86.7%,the single BAPN group was a little lower. None dissecting aorta was detected in the controlgroup. Single BAPN group mice aortic wall show aortic aneurysm model changeConclusion BAPN combine with AngⅡwill be successful and efficient in inducing theaortic dissection in FVB mice, single BAPN group show a little lower incidence.Part2Detection of Autophagy-related Protein in theaortic tissue from Aortic Dissection miceObject Explore autophagy related protein and mRNA expression in the aortic tissue fromaortic dissection mice. Our destination is providing provide foundation and basis for thefurther exploration of the role of autophagy on the pathogenesis of acute aortic dissection.Method By RT-PCR and immunohistochemistry staining, the expression of autophagy-related protein, such as LC3B, Beclin1was detected quantitative and semi-quantitative.Outcome The expression of LC3B, Beclin1in the aortic tissue from aortic dissection miceis significantly higher than the control group (P <0.05). The LC3B, Beclin1main located inthe middle of aorta according to the immunohistochemistry.Conclusion The incidence of aortic dissection in our animal model may have a strongrelationship with the incidence of autophagy in VSMC.Part3Detection of Autophagy-related Gene andProtein in AngⅡ or BAPN-treated VSMCObject Detect the expression of Autophagy-related Protein in VSMC stimulated by AngⅡ Method First, we use AngⅡ and BAPN to stimulate the Rat-VSMC respectively by24hand48h; then we use RT-PCR to detect the expression of autophagy-related protein in VSMC.Outcome Treated by the concentration of10-4mol/L,10-5mol/L and10-6mol/L AngⅡ,10-4mol/L BAPN, autophagy in VSMC will be induced. Treated by10-2mol/L for48h, a lowlevel autophagy will be induced too.Conclusion AngⅡ can induce VSMC autophagy occurs, and this kind of autophagy mayparticipate in the occurrence of the aortic dissection. BAPN alone may induce a lowautophagy in Rat-VSMC. |
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