A Clinical And Animal Study On The Associations Between The Pattern Of Syndrome Of Traditional Chinese Medicine And Polymorphism Of Apolipoprotein E Gene In Corcnary Atherosclerotic Heart Disease Treated With Tong Xin Luo Capsule

Objective:1.To probe the hereditary susceptibility of coronary atherosclerotic heart disease(CHD) by analyzing Apolipoprotein E(ApoE) Gene.2.To find the possibility of Traditional Chinese Medicine and Polymorphism of ApoE Gene in CHD.3.On the base of Polymorphism of ApoE Gene in CHD interfered by Tong Xin Luo Capsule to find its molecular mechanism on treating CHD.4.To detect the effects of Tong Xin Luo Capsule on the Pattern of Syndrome of Traditional Chinese Medicine focused on Polymorphism of ApoE Gene in CHD.Methods:1.Clinical Research:All 118 standard patients come from the out-patient department of Jingsu Provincial Hospital of TCM from Mar.2006 to Dec.2007.They are experiment group and the other 128 healty adults belong to control group.Through gene sequencing of blood samples and DNA sequencing analysis to determine?ApoE phenotype distribution and allele frequency.?TC,TG,HDL-C,LDL-C and HDL-C with automatic biochemistry analyzer.2.Animal Research:40 ApoE(-/-) mice hyperlipemia and AS model were successfully established.They are divided by 5 groups randomly with additional 8 isogenetic mice as control group.TC?TG?HDL-C?LDL-C,TXB2?6-Keto-PGF1??ET?CEC?of blood samples,pathohistological evaluations of plague in CHAD of mice and MMP1,MMP9 level in serum were detected. 3.Statistical analysis:In evaluating significance,the X~2 was used.In relevant cases,the significance of differences between data sets is highlighted pp0.05.Statistical analysis was done with SAS software.Results:1.3 kinds of homozygote and 3 kinds of heterozygote of 118 CHD patients,namely E2/2?E3/3?E4/4 were detected,among most of which are ApoE gene phenotype.The genotypic frequency of E2/4,E3/4,E4/4 in experiment groups increased than those of control group (X~2=5.004,P?0.05).The genotypic frequency of E3/3 in experiment groups decreased than those of control group(X~2=6.8743,P?0.01).Compared with 123 samples of control group,the genotypic frequency of?3 allele decreased significantly(X~2=9.2898,P?0.05) and which of?4 allele increased significantly(X~2=13.927,P?0.01).2.The highly proportion of E2/4+E3/4+E4/4 genotypic frequency in 118 CHD patients belongs to ariac blood stasis,tanzuo impotency and deficiency of both vital energy and yin(82.93%),followed by E3/3 genotypic frequency(75.00%) and E2/2+E2/3 genotypic frequency(61.90%)of which is the lowest.The proportion of genotypic frequency in pattern of syndrome of Traditional Chinese Medicine(TCM) of ariac blood stasis,tanzuo impotency and deficiency of both vital energy and yin is significant different to that cold accumulation of heart meridian,deficiency of heart and kidney -YIN and deficient and weak YANG QI(P?0.05),among which the genotypic frequency of?4 allele increased significantly and?2 with?3 is equally.3.Tong Xin Luo Capsule can enhance significantly of pattern of syndrome of TCM of ariac blood stasis,tanzuo impotency and deficiency of both vital energy and yin ApoE in the genotypic frequency of?2,?3,?4(p?0.05),among which the tanzuo impotency got the best effects.The best results can also get in the genotypic frequency of?4.The level of TC,TG,HDL-C and LDL-C in the groups interfered with Tong Xin Luo Capsule improved significantly than those of control groups(p?0.05).4.The effects of Tong Xin Luo Capsule on ApoE(-/-) mice hyperlipemia and AS model are:?The levels of TC,TG and LDL-C in the groups interfered with high dose of Tong Xin Luo Capsule increased than those of controls and The level of HDL-C decreased significantly(p?0.05 or p?0.01) without the positive results in the groups interfered with low dose of Tong Xin Luo Capsule(p?0.05).?The sores of pathohistological evaluations of plague in CHAD of mice in the high dose of Tong Xin Luo Capsule is 1.7�2.06 decreased significant than that of model groups which is 4.0�1.76(P?0.01) and better than positive control group interfered with Simvastatin(P?0.05).?The levels of,TXB2?6-Keto-PGF1?of blood samples in ApoE(-/-) mice interfered with Tong Xin Luo Capsule did not change enough compared with those of control groups.The level of ET is lower in Tong Xin Luo Capsule group than that in control ones(P?0.05).The level CEC decreased at week 4,8 and 12 than that of control groups(P?0.05 or P?0.01).The level of MMP1 and MMP9 decreased compared with the level of TIMP-1 increased in the Tong Xin Luo Capsule interfered groups(P?0.05 or P?0.01).Conclusions:1.The main patterns of syndrome of TCM are ariac blood stasis,tanzuo impotency and deficiency of both vital energy and yin.2.The gene?4 allele is the susceptive allele in CHD and the important factor of genetic liability.3.The gene?3 allele can be a protective factor on CHD occurrence.4.Polymorphism of ApoE gene in CHD can interfere the occurrence of CHD by way of influencing metabolism of blood fat.5.The general effects of Tong Xin Luo Capsule on CHD are significant,especially on the patterns of syndrome of TCM which are ariac blood stasis,tanzuo impotency and deficiency of both vital energy and yin and the best of which is tanzuo impotency.In addition,the effects of Tong Xin Luo Capsule on the decrease of the level of TC?LDL-C and the increase of the level of HDL�C are also notable.6.Tong Xin Luo Capsule can reduce AS by interfering metabolism of blood fats and reducing the injury of vascular endothelial cells,enhancing their function and inhibiting the function of inflammatory factors.7.It will be of important interests of early prevention,monitor and cure of CHD by detection of polymorphism of ApoE gene among people.8.The treatments with the methods of TCM can effectively ameliorate the clinical symptoms and improve the effects on CHD.