| Part one: The experimental study of effective components compatibility of Qixuebingzhi (QXBZ) compound formula on prevention and treatment of atherosclerosis (AS) in rabbit model.Objective: This experiment was designed to investigate the effect and mechanism of effective components extracted from QXBZ compound formula compatibility on prevention and treatment AS in the rabbit model. Methods: Sixty male Japan White rabbits were injected bovine serum albumin and fed with high lipid food for 7 days then they were randomly divided into 6 groups: ①sham group;②control group;③total extract of QXBZ compound formula group (total extract group);④D, E effective components compatibility (DE group. D extract mainly consisted of paeoniflorin, while E extract mainly consisted of total flavonoids. The ratio of D and E is 1:1);⑤D, E optimized compatibility group (The ratio of D and E is 1:2);⑥Simvastatin group. All rabbits were administered with corresponding drugs for 10 weeks. The aorta pathological changes, the level of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL), apolipoprotein, platelet aggregation, interleukin-6 (IL-6), interleukin-8 (IL-8), endothelin (ET), alcitonin gene-related peptide (CGRP), thromboxane B2 (TXB2), 6-ketone-prostacyclin (6-Keto-PGF1a), plasma renin activity (PRA), angiotensin II (Angll), nitrogen monoxidum (NO) and Lectin-like oxidized LDL receptor-1 (LOX-1) mRNA expression in aorta, etc, were mearsured. Results: Ten weeks after modeling, electron microscope observation on the aorta in control group showed the typical pathological changes of AS, intercellular space obviously increased and endothelial cell's membrane discontinued;the serum lipid, apolipoprotein, vasoactive substance (ET, TXB2, PRA, Angll) level elevated;platelet aggregated and inflammation markers levels increased, all above changes represented characters of AS. The aorta pathological and vascular endothelial cell changes of AS in all treatment groups' showed better than control group. The score of aorta plaque significantly decreased in all treatment groups compared with control group (P<0.01, P<0.05);area of plaque, plaque/lumina area rate, maximum intima thickness in total extract group, DE group and DE optimized group decreased as compared with control group (P<0.01, P<0.05);there was no significant difference in lumina area and intima/media rate between groups (P>0.05). Serum lipid levels were higher in control group and in all treatment groups than that in sham group (P<0.01);compared with control group, TC significantly decreased in DE group (P<0.01);TG significantly decreased in DE group and in DE optimized group (P<0.05), HDL and LDL-C decreased in all treatment groups (P<0.05, P<0.01), VLDL decreased in total extract group and in DE group than that in control group (P<0.01). There were significantly higher ApoB and ApoAI levels in control group and in all treatment groups than that in sham group;compared with control group, serum ApoB and ApoAI levels were obviously lower in all treatment groups (P<0.05, P<0.01). Aorta LOX-1 significantly expressed in control group and in all treatment groups, and there were depressed LOX-1 mRNA expression in total extract group and in DE group than that in control group. ET was higher in control group than that in sham group (P<0.01);compared with control group, there were decreased ET level in all treatment groups (P<0.05, P<0.01), but there was no difference between all treatment groups (P>0.05). There were increased trend of CGRP in all treatment groups than that in control group (P>0.05). NO was significantly lower in control group than that in sham group (P<0.01), NO were significantly higher in all treatment groups than that in control group (P<0.01). TXB2 was significantly higher in control group than that in sham group (P<0.01), all the component compatibility groups TXB2 levels significantly decreased than control group (P<0.05> P<0.01), but there was no significantly difference between all treatment groups (P>0.05). 6-Keto-PGFla in DE optimized group was significantly higher than that in control group (P<0.05), but there was no difference between all treatment groups (P>0.05). PRA and Angll were significantly higher in control group than that in sham group (P<0.01), all treatment groups PRA and Angll levels significantly decreased than control group (P<0.05, P<0.01), but there was no significant difference between all treatment groups (P>0.05). IL-6, 8 were significantly higher in control group than that in sham group (P<0.05), IL-6 in total extract group and in simvastatin group were significantly lower than that in control group (P<0.05> P<0.01);IL-8 in total extract group was significantly lower than that in control group (P<0.05), in other groups there was only lowering trend (P>0.05). The 1,3,5 minute platelet aggregation rate and maximum platelet agglutination rate (MPAG) were significantly higher in control group than that in sham group (P<0.01), 3 minute platelet aggregation rate was significantly lower in total extract group than that in control group (P<0.05), 1 minute platelet aggregation rate was significantly lower in DE group than that in control group (P<0.05), MPAG in total extract group, in DE group and in simvastatin group was significantly lower than that in control group (P<0.05). Conclusion: Combination of immunologic injury and high lipid fed could make AS formation of Japan White rabbits. QXBZ compound formula was effective toprevent and treat AS. D, E effective components (the rate of D and E is 1:1), could basically achieve the effect of primary QXBZ compound formula. DE group and total extract group played important role in reducing and stabilizing AS plaque. If drugs for regulating QI increased in the effective components compatibility, such as DE optimized group, the effect on vasoactive substance was obvious;the regulatory effect on inflammation mediator was only found in primary QXBZ group. In a word, the mechanisms of effective components compatibility of QXBZ compound formula involved in different targets, by which it exerted potential benefit for preventing and treating AS.Part two: Effect of QXBZ compound formula to prevent restenosis after carotid artery stenting (CAS).Objective: In present study, the effect of QXBZ compound formula to restenosis after CAS was observed. Method: 32 carotid stenosis in hospital patients were selected from October 2003 to June 2005, all patients were diagnosed by carotid arteriography with more than 50% stenosis either in common carotid artery or internal carotid artery, meanwhile, they had also diagnosed with traditional Chinese medicine vertigo. After CAS, the 32 patients were randomly divided into control group (15 cases) and QXBZ group (17 cases). Patients in control group were given conventional treatment of westen medicine, in QXBZ group were added capsuled QXBZ compound formula. Restenosis of in-stent 12 months after CAS, clinical symptoms, serum lipid and safety targets were observed. Results: 35 patients were selected, stents were successfully implanted in 32 case and 3 case technical failure. 34 self-expanding stents were applied. After operation the degree of stenosis improved significantly. Distal end protectors were used in all patients before stents implantation. There was no serious complications in the operation process. Restenosis of in-stent were found in 6 cases 12 months after operation through ultrasound or angiography. Among these cases, 3 were found more chan 50% restenosis. Restenosis rate in QXBZ group (11.76%) were significantly lower than that in control group (26.67%) (P<0.05). Transient ischemia attach (TLA) were significantly lower than that in control group (P<0.05), while no difference in other clinical symptoms in groups. Twelve months after CAS serum TC and ox-LDL in QXBZ group decreased as compared with control group. Conclusion: After CAS, QXBZ compound formula decreased the rate of restenosis of in-stent, depressd serum TC and ox-LDL levels, reduced TLA during 12 months.Part three: Effect of QXBZ compound formula on treatment of arteriosclerosis obliterans (ASO) patients with femoral-poplital arterial bypass.Objective: The present trial was designed to observe the clinical effects of QXBZ compound formula on treatment of ASO patients with femoral-poplital arterial bypass. Methods: 38 ASO in hospital patients selected from October 2003 to March 2005 were randomly divided into control group (18 cases, 20 limbs) and QXBZ group (20 cases, 21 limbs). All patients were diagnosed ASO degree II -IV, meanwhile with diagnosed traditional Chinese medicine cellulitis. All patients were diagnosed by arteriography with superficial femoral artery occlusion and treated with femoral-poplital arterial bypass. After operation, patients in control group were given conventional treatment of westen medicine, in QXBZ group were added capsuled QXBZ compound formula for 3 months. Clinical symptoms, ankle brachial index (ABI), vascular prosthesis condition, serum lipid, blood coagulation and safety targets were observed. Results: Thirty eight cases (41 limbs) were operated with femoral-poplital arterial bypass, 26 cases associated with endarterectomy. The success rate of operation were 100%. After operation, all clinical symptoms improved. All 38 cases were followed up for average 21 months. INR was kept 2.5-3 using Warfarin anticoagulation in all patients. Twelve months after operation, the traditional Chinese medicine score, the amputation ratio and intermittent claudication in QXBZ group were significantly lower than that in control group (P<0.05);ABI and vascular prosthesis patency rate in 6 month and 12 months improved in QXBZ group than that in control group (P<0.05). Twelve months after operation serum TC, LDL, TG decreased in all patients, and there is significant difference in QXBZ group compred with pre-operation (P<0.05). No obvious adverse side-effect was found. Conclusion: Twelve months after femoral-poplital arterial bypass, combination with the conventional treatment, QXBZ compound formula decreased amputation rate and intermittent claudication, improved ABI and vascular prosthesis patency rate, increased tissue blood perfusion and improved limb ischemia symptoms in ASO patients.
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