| Objective: To observe the effect of Xin’an prescription Danzhijiangtang Capsule(DJC) with Yiqi Yangyin Huoxue Tongluo effectiveness on serum MMP-9, TIMP-1,sTM level as well as the carotid IMT and plaque score in type2diabetes mellitus(T2DM) patients. Meanwhile, to research the effectt of DJC on the model of T2DMwith atherosclerosis in rats on expression of thoracic aortic MMP-9mRNA, TIMP-1mRNA by molecular gene level. To discuss vascular protective effects mechanism ofXin’an prescription DJC on T2DM macroangiopathy body.Methods:1. Clinical Research:70T2DM patients with macroangiopathy were randomly and equally divided into2groups. The control group were given conventional oral hypoglycemic drugs combinedwith atorvastatin treatment, and the treatment group were given DJC based on thecontrol group therapy. Both two groups were treated for12months. All patients wereaccompanied with deficiency of qi and yin and stagnation of blood. Measured FPG,2hPG, HbA1c, insulin, serum MMP-9, TIMP-1, sTM levels and to observe the changesof carotid IMT and plaque scores before and after treatment.2. Experiment:60male SD rats were fed one week for adaptation, and randomly divided into2groups: Blank group (n=10, rats were fed with routine food) and diabetes mellitus group(n=50, rats were fed with high-fat diet). Diabetes mellitus group were given a total doseof700thousand units of Vitamin D3within3days to contribute to the model of AS rats.After4weeks, rats were injected with small dose of streptozotocin (STZ) to inducedmodel of T2DM with AS in rats. Rats were tested glucose and41rats were diagnosed asT2DM with AS finally, then they were randomly divided into4groups again: modelgroup (n=8), low dose group (n=11), middle dose group (n=11) and high dose group(n=11). The blank group and model group were given physiological saline, other groups were treated by gavage of DJC with different doses for12weeks. To observe thebehavior of rats and weight change before and after treatment. At the end of experiment,collect blood to test FPG, FPG,2hPG, TC and TG. The level of MMP-9, TIMP-1andsTM were tested by ELISA. While the thoracic aortic tissue were removed to testMMP-1and TIMP-1mRNAby RT-PCR.Results:1. Clinical Research:The clinical research showed that the total efficiency of treatment group had provedmuch better (91.18%) than the control group (67.74%)(P<0.05). TCM integralSyndrome of treatment group was better than normal control group (P<0.01), and it hadsignificance to compared with pre-treatment (P<0.01).After treatment, compared with pre-treatment, we found the contents of FPG,2hPG,2hINS, HbA1c, TG, LDL and HDL in both control group and treatment group decreased(P<0.05or P<0.01). Moreover, compared with control group, the content of2hPG,2hINS, HbA1c, TG and LDL in treatment group was significantly different (P<0.05orP<0.01). After treatment, two groups with carotid IMT and plaque scores weresignificantly different compared with pre-treatment (P<0.01), the content of carotidIMT in treatment group decreased compared with control group (P<0.05) while theplaque scores was no significant difference compared with control group (P>0.05).After treatment, the levels of MMP-9decreased to compared with pre-treatment(P<0.01), and treatment group decreased obviously than that in control group (P<0.01).The levels of TIMP-1increased to compared with pre-treatment (P<0.05or P<0.01),and treatment group decreased obviously than that in control group (P<0.01).2. Experiments：Weight of rats in low, middle and high dose groups were higher than before(P<0.01). After treatment, FPG of rats in low, middle and high dose groups decreasedmuch more than those of model group (P<0.01). There was statistical significance of TG, HDL and LDL in low, middle and high dose groups compared with model group(P<0.05or P<0.01). The serum MMP-9, TIMP-1and sTM levels in model, low, middleand high dose groups were higher than those of blank group (P<0.01), compared withmodel group, MMP-9and sTM levels were decreased while TIMP-1increased in low,middle and high dose groups (P<0.01). The expression of MMP-9and TIMP-1mRNAin model, low, middle and high dose groups were significantly higher than that in blankgroup (P<0.01). The expression of MMP-9mRNA in low, middle and high dose groupswere lower than of model group (P<0.01), moreover, TIMP-1mRNA in high dosegroup expressed higher than low dose group (P<0.05).Conclusion:Xin’an prescription of DJC can improve the clinical symptoms markedly and reversecarotid atherosclerosis partly. It shows that DJC has a protective effect on diabeticmacroangiopathy. The possible mechanisms maybe: to reduce glucose, improve insulinresistance; regulate lipid metabolism, to infect the vascular endothelial functions; toreduce the levels of MMP-9, sTM and increase the level of TIMP-1; to keep MMP-9mRNAand TIMP-1mRNAexpression balance; reduce carotid artery IMT. |
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