The Curative Effect Comparison And The Possible Mechanism Of Alpha Lipoic Acid And Salvia Miltiorrhiza On Diabeteic Lower Extremity Arterial Disease

[background]In recent years, the incidence of diabetes increased year by year, diabetes complications are also increasing. Diabetes concurrent lower limb vascular lesions (diabetic lower extremity arterial disease, DLEAD) are7to10times as patients with diabetes mellitus. Some patients are diagnosed diabetes that already exist, and inctrease with the growth of age, duration. Common symptom is intermittent claudication, performance of one body motion pain, discomfort, or fatigue, after the break to alleviate. Only a third of the DLEAD patients with typical intermittent limp symptoms,>50%of patients without symptoms or atypical symptoms, the rest DLEAD patients with severe symptoms, by resting pain, gangrene or gangrene. But since there are patients peripheral neuropathy, body feeling decline, DLEAD symptoms of diabetes more often not obvious, the only show are lower limbs on foot, fatigue or slow down, etc. DLEAD patients pathological changes is more serious than patients with the lower extremities diabetes lower limb artery disease,and more diffuse disease extent, more easily to limbs far end development. Whether to diabetic patients or those withoutdiabetes, lower limb artery disease is the main factor of limb amputations, even if patients are without symptoms, lower limb artery disease is the the sign of whole body cardiovascular and cerebrovascular diseases. So early detection of diabetes lower limb vascular disease, early intervention treatment, can reduce the clinical symptoms and reduce the DLEAD clinical morbidity and amputation rate, the incidence of cardiovascular events, and improve the quality of life of the patients, improve the long-term prognosis.the treatment of Diabetes lower limbs of vascular lesions t is various, to alleviate the symptoms, slow down the process of atherosclerosis and control risk factors is the principle, inncluding surgery, interventional treatment, medical treatment, etc. Medical treatment includes the control of the risk factors, such as quit smoking, reduce body quality, step-down, fall fat, control blood sugar, etc.,anti-platelet therapy, such as aspirin, clopidogrel, application of vessels to dilate drug therapy, and so on.Lipoic acid (LA) also called alpha lipoic acid (ALA), is a natural two sulfur compounds, in body,which can be transformed for the two hydrogen lipoic acid (DHLA, reduced), LA and DHLA both have the very strong oxidation resistance, they in body, synergy, is known to be one of the strongest effectin natural antioxidants. Research shows that lipoic acid that atherosclerosis plasma fiber melts the patients with plasminogen activator inhibitor1(PAI-1), interleukin (IL)-6, reduce inflammation factors, lipid oxidation end-products of MDA reduce, GSH increase, so as to reduce oxidatie stress level,andimprove NO mediated diastolic blood vessels, improving the function of endothelial cells.Salvia miltiorrhiza Bunge, the main effective ingredients are such as for Dan CanTong fat soluble constituents and Dan phenolic acids water-soluble ingredients such as two parts. The pharmacological research results show that salvia miltiorrhiza has dilating coronary artery, increase coronary blood flow, prevent myocardial ischemia, microcirculation, fall hematic fat, etc.The primarily diastolic function damage of Diabetes vascular lesions with endothelial dependence may be diabetes vascular lesions occurr tumor-initiating factors and the fundamental pathological physiology change, the core for endothelial cells of dysfunction. Endothelial cells and vascular smooth muscle blood is an important barrier between, the secretion of various active substances in precision balance, and maintain normal physiological function of blood vessels. When endothelial function disorder makes the secretory activity material imbalanceed, the pathological changes cause blood vessels leision. Patients with diabetes to promote inflammation factors interleukin (inter-leukin IL)-1,6, active oxygen (reactive oxygen spicies, ROS) c-reactive protein (C-reactive protein, CRP) express significantly increased, promote adhesion molecule expression, increase inflammation and solidification chemotactic agent protein (PAI-1, fibrinolytic enzyme that the activation and tissue factor) secretion, induction blood vessels that regulation (endothelial NO gentle shock peptide) release, cause blood vessel function damage.How do alpha-lipoic acid and Salvia miltiorrhiza improve the clinicial symptoms of diabetic patients with vascular lesions? what is the effect of the above two drugs on oxidative stress factors, such as GSH,MDA of diabetic patients with lower extremities vascular lesions? what is the effect of the above two drugs on inflammatory factors:plasma fiber melts the enzyme activators-1, interleukin (il)6, The past research has not been concerned.Based on the above thinking, this experiment is divided into four parts. This experiment is to compare clinical effect of alpha lipoic acid and Salvia miltiorrhiza on patients with lower extremities vascular lesions, and inflammation factors and oxidative stress and related factors are discussed.Part1:clinical curative effect observation of alpha lipoic acid and salvia miltiorrhiza on the treatment of diabetes lower limb vascular lesions[objective]Observation the clinical clinical curative effect of alpha lipoic acid and Salvia miltiorrhiza on diabetes with vascular lesions of lower extremities.[methods]1. Diabetic patients with vascular lesions work as the research object, eliminate those whose heart, liver and kidney function is not complete. Which conform to the 1999WHO diabetes diagnosis standard. ABI<0.9. All insulin after admission control blood sugar.2. After admission measure blood pressure, body mass index (BMI), fasting blood sugar, blood fat, the glycated hemoglobin (HbA1C), etc.3. Group:1) a-lipoic acid±salvia miltiorrhiza group (group A, n=20, a-lipoic acid600mg/d,iv by drip andSalvia miltiorrhiza,40mg/d,iv by drip,21days)2) salvia miltiorrhiza group (group B, n=20, SalviamiltiorrhizaBunge,40mg/d,iv by drip,21days).4. According to the clinical symptom scores, observe the clinical scoring change of the three group self before and after treatment.5. According to clinical symptom scores, observe the clinical scoring change of the two groups before and after treatment.6. According to WIQ score, observe the clinical scoring change before and after treatment.[results]1. WIQ scores were not significant different between the two groups (P>0.05)2. WIQ scores were significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001) Group B was significant different before and after treatment,(P<0.001) respectively.3. WIQ scores were significant different between the two groups before and after treatment. Group A was higher than group B (P<0.001)4. Clinical symptom scores were not significant different between the two groups before treatment (P>0.05)5. Clinical symptom scores were significant different before and after treatment of the two groups. Numbness:Group A was significant different before and after treatment,(P<0.001), Group B was significant different before and after treatment,(P=0.008), respectively, cold:Group A was significant different before and after treatment,(P<0.001), Group B was significant different before and after treatment, (P=0.008), rest pain:Group A was significant different before and after treatment,(P<0.001), Group B was significant different before and after treatment,(P=0.005), respectively.6. Clinical symptom scores were significant different before and after treatment between the two groups (P<0.05). Numbness:Group A was higher than group B (P=0.002).Cold:Group A was higher than group B (P=0.004). Rest pain:Group A was lower than group B (P=0.002), respectively.[conclusion]1. WIQ scores of diabetic patients with vascular lesions were significant improved after correcting of metabolic disorder.2. WIQ scores of diabetic patients with vascular lesions were improved by using of alpha lipoic acid plusSalvia miltiorrhiza.3. WIQ scores of diabetic patients with vascular lesions were improved by using ofSalvia miltiorrhiza. But alpha lipoic acid plusSalvia miltiorrhiza are better thanSalvia miltiorrhiza according WIQ scores improving,4. Clinical symptom scores of diabetic patients with vascular lesions were improved by using of alpha lipoic acid plusSalvia miltiorrhiz.5. Clinical symptom scores of diabetic patients with vascular lesions were improved by using ofSalvia miltiorrhiza. But Alpha lipoic acid plus Salvia miltiorrhiza Bunge was better thanSalvia miltiorrhiza according Clinical symptom scores improving. Part2:alpha lipoic acid and salvia miltiorrhiza mediated flood mediated diastolic function of diabetic patients with lower extremities vascular lesion. [objective]Observe the influence of diastolic function of vascular endothelial dependent alpha lipoic acid andSalvia miltiorrhiza on diabetic patients with lower extremities vascular lesions.[methods]1. Diabetic patients with vascular lesions work as the research object, and eliminate those whose heart, liver and kidney function is not complete. Which conform to the1999WHO diabetes diagnosis standard. ABI<0.9.2. Group:1) lipoic acid+salvia miltiorrhiza group (group A, n=20)2) salvia miltiorrhiza group (group B, n=20).3.The12MHz high frequency line of probe array of color doppler ultrasound diagnostic instrument was used to measure the diameter of humerus artery diastolic blood vessels.4.Use pneumatic tourniquet to takes type of blood pressure300mmHg for4-5minutes, quickly deflated, the cuff was released after60-45second at the same area and measure the inner diameter of diastolic blood vessels.[results]1. The diameter and flow velocity of humerus artery diastolic blood vessels was not significant different between the two groups before treatment (P>0.05)2. FMD was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001).Group B was significant different before and after treatment (P<0.001), respectively.3. FMD was significant different between the two groups before and after treatment. Group A was higher than group B (P<0.001)[conclusion]1. FMD of diabetic patients with vascular lesions was significant improved after correcting of metabolic disorder.2. FMD of diabetic patients with vascular lesions were improved by using of alpha lipoic acid plusSalvia miltiorrhiza. 3. FMD of diabetic patients with vascular lesions were improved by using ofSalvia miltiorrhiza.But alpha lipoic acid plusSalvia miltiorrhiza are better thanSalvia miltiorrhiza according FMD improving. Part3:Influence of alpha lipoic acid and salvia miltiorrhiza on oxidative stress factors of diabetes with lower extremities vascular lesions[objective]Observation how alpha lipoic acid influent serum oxidative stress factors of diabetic patients with lower extremities vascular lesions and comparing withSalvia miltiorrhiza.[methods]1. Diabetic patients with vascular lesions wok as the research object, persons of whom heart, liver and kidney function is not complete are eliminated. Which conform to the1999WHO diabetes diagnosis standard. ABI<0.9.2. Group:1) lipoic acid+salvia miltiorrhiza group (1group, n=20)2) salvia miltiorrhiza group (2groups, n=20).3. The content and the method to determine the inflicting MDA.4. Determine GSH.[results]1. GSH concentration was not significant different between the two groups before treatment (P>0.05)2. GSH concentration was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001) Group B was significant different before and after treatment,(P<0.001) respectively.3. GSH concentration was significant different between the two groups before and after treatment. Group A was higher than group B (P<0.001) 4. MDA concentration was not significant different between the two groups before treatment (P>0.05)5. MDA concentration was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001), Group B was significant different before and after treatment,(P<0.001), respectively.6. MDA concentration was significant different between the two groups before and after treatment. Group A was lower than group B (P<0.001)[conclusion]1. GSH concentration of diabetic patients with vascular lesions was significant high after correcting of metabolic disorder, meanwhile, MDA concentration of diabetic patients with vascular lesions was significant low.2. GSH concentration was high after using of alpha lipoic acid plus salvia miltiorrhiza.3. GSH concentration was high after using of alpha lipoic acid plus salvia miltiorrhiza. But alpha lipoic acid plus salvia miltiorrhiza was better than salvia miltiorrhiza according GSH concentration improving.4. MDA concentration was low after using of alpha lipoic acid plus salvia miltiorrhiza.5. MDA concentration was low after using of salvia miltiorrhiza.But alpha lipoic acid plus salvia miltiorrhiza was better than salvia miltiorrhiza according MDA concentration reducing. Part4:Influlence of inflammation factors of alpha lipoic acid and salvia miltiorrhiza on diabetic patients with lower extremities vascular lesions [objective]Observation inflammation factors of alpha lipoic acid lower extremities to diabetic patients with vascular lesions and the comparison with prostaglandin E1.[methods]1. Diabetic patients with vascular lesions perform as the research object,and eliminate those whose heart, liver and kidney function is not complete. Which conform to the1999WHO diabetes diagnosis standard. ABI<0.9.2. Group:1) lipoic acid+salvia miltiorrhiza group (1group, n=20)2) salvia miltiorrhiza group (2groups, n=20).3. Use Elisa test plasma IL-6.4. Use Elisa test plasma VCAM-1.5. Use Elisa test plasma PAI-1.[results]1. IL-6concentration was not significant different between the two groups before treatment (P>0.05)2. IL-6concentration was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P=0.001), Group B was significant different before and after treatment,(P=0.010)3. IL-6concentration was significant different between the two groups before and after treatment. Group A was lower than group B (P<0.001)4. VCAM-1concentration was not significant different between the two groups before treatment (P>0.05)5. VCAM-1concentration was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001), Group B was significant different before and after treatment,(P<0.001) respectively.6. VCAM-1concentration was significant different between the two groups before and after treatment (P<0.001). Group A was lower than group B. 7. PAI-1concentration was not significant different between the two groups before treatment (P>0.05)8. PAI-1concentration was significant different before and after treatment of the two groups.Group A was significant different before and after treatment,(P<0.001) Group B was significant different before and after treatment,(P<0.001) respectively.9. PAI-1concentration was significant different between the two groups before and after treatment (P<0.001). Group A was lower than group B.[conclusion]1. IL-6,VCAM-1,PAI-1concentration of diabetic patients with vascular lesions was significant low after correcting of metabolic disorder,2. IL-6concentration was low after using of alpha lipoic acid plus salvia miltiorrhiza.3. IL-6concentration was low after using of salvia miltiorrhiza.But alpha lipoic acid plus salvia miltiorrhiza were better than salvia miltiorrhiza according IL-6concentration reducing.4. VCAM-1concentration was low after using of alpha lipoic acid plus salvia miltiorrhiza.5. VCAM-1concentration was low after using of salvia miltiorrhiza. But alpha lipoic acid plus salvia miltiorrhiza were better than salvia miltiorrhiza according VCAM-1concentration reducing.6. PAI-1concentration was low after using of alpha lipoic acid plus salvia miltiorrhiza.7. PAI-1concentration was low after using of salvia miltiorrhiza. But alpha lipoic acid plus salvia miltiorrhiza were better than salvia miltiorrhiza according PAI-1concentration reducing.