| Arteriosclerosis obliterans (ASO) is a common disease with high prevalence in vascular surgery. In traditional Chinese medicine (TCM) surgery, the disease is categorized under the area of "digital gangrene". TCM has a long history in diagnosis and treatment of digital gangrene, and its Chinese medicine treatment has been consistently developing over the ages. However, research targeted at digital gangrene TCM intervention and its correlation with gaseous signaling molecules is relatively few. In this study, our objectives can be concluded into three main sections:1) studying the correlation between digital gangrene and replenishing qi activating blood method, as well as the correlation between ASO and gaseous signaling molecules,2) observation of therapeutic efficacy in the treatment of qi deficiency blood stasis pattern using vessel collateral dredging stasis decoction,3) observation of the regulatory effects of vessel collateral dredging stasis decoction on gaseous signaling molecules in ASO rats.The first section: literature review. Literature related to digital gangrene’s disease cause and mechanism of disease, treatment of digi tal gangrene using qi replenishing blood activating method, modern medical research on ASO, relationship between gaseous signaling molecules and arteriosclerotic disease were reviewed.The second section: experimental research. Research on vessel collateral dredging stasis decoction’s intervening effects in qi deficiency blood stasis pattern rat models, and its regulatory mechanism on gaseous signaling molecules were conducted.Methods:50lab rats were randomly distributed into5groups: blank control group (A),10rats; model group (B),10rats; low dosage treatment group (C),10rats; middle dosage treatment group (D),10rats; high dosage treatment group (E),10rats. The rats were subjected to composite factors comprising high-fat diet, starvation and fatigue in order to construct qi deficiency blood stasis rat models. Experimental period was set as12weeks.Observation of morphology and symptomatology changes in qi deficiency blood stasis rat models.Using the vessel collateral dredging stasis decoction, a clinically proven formula by Professor Pang He, rats from the respective treatment groups were administered with low dosage (1g/Kg), middle dosage (2g/Kg) and high dosage (3g/Kg) drug treatments accordingly. Drug treatment was administered for a period of4weeks.Monitoring of general indicators:Blood coagulation function, blood lipid level, blood glucose (GLU) level, liver function and kidney function were monitored. The results were then used as indicators for safety evaluation. Therapeutic effect was also evaluated.Chromatography was used to detect content of gaseous signaling molecules hydrogen sulphide (H2S), nitric oxide (NO) and inducible nitric oxide synthase (iNOS).Radioimmunoassay analysis was used to detect expression of vasoactive substances endothelin (ET) and vegetative growth factor (VEGF)Histopathological changes were observed.Results:Effects of vessel collateral dredging stasis decoction on low density lipoprotein (LDL) and blood GLU levels in ASO rats:Compared to the blank control group, significant increase in LDL and blood GLU levels were observed in model group rats. Difference in LDL and blood GLU levels was statistically significant. As drug dosage increases, progressive decrease in blood GLU levels eventually leading to normal levels was observed. Significant difference was observed between the high dosage treatment group and model group. Although no significant progressive decrease was observed for LDL levels, LDL levels in all three treatment groups recovered to normal or lower than normal levels. Statistical analysis of its change indicator revealed significant difference.Effects of vessel collateral dredging stasis decoction on H2S levels in ASO rats:Compared to the blank control group, a significantly different decrease in H2S levels was observed in model group rats. As the drug dosage increases, progressive increase in H2S was observed, along with a similar increasing trend in related indicators from the artery homogenate. Difference between the high dosage treatment group and model group was statistically significant.Effects of vessel collateral dredging stasis decoction on BT and VEGF levels in ASO rats:Compared to the blank control group, in blood serum ET, blood serum VEGF and artery homogenate ET levels in model group rats were statistically significant. Compared to the model group, progressive decrease was observed in blood serum and artery homogenate ET levels as drug dosage increased. Blood serum VEGF values however, displayed progressive increase as drug dosage increased. Significant difference was observed for change indicators in the data from each group.Conclusion:Through composite factor method using high-fat diet, starvation and fatigue, digital gangrene qi deficiency blood stasis rat models can be reproduced.Digital gangrene qi deficiency blood stasis rat model:Morphology changes included darkening and drying up of fur, decrease in body weight increasing rate, weakening of exercise capacity etc. Symptomatology changes include decrease in food intake, slower response, and purplish-dark claw and tail coloration.Treatment of digital gangrene qi deficiency blood stasis rats using qi replenishing blood activating method improves its organ functions, regulates GLU and lipid metabolism, decreases LDL and blood GLU levels, and controls arteriosclerosis (AS) risk factors.In ASO formation, H2S displays a decreasing trend. After TCM qi replenishing blood activating treatment, H2S levels increased, thereby suggesting that biological effects of H2S may be the intrinsic mechanism in qi replenishing blood activating TCM treatment of digital gangrene.ET, a biological substance produced and secreted by vascular endothelial cells, is one of the early discovered long-acting vasoconstrictors. On the other hand, VEGF is a type of endothelial growth factor widely-used in clinical treatment, and is known to promote limb collateral circulation formation. In our study, we have shown that treatment of digital gangrene qi deficiency blood stasis rats using qi replenishing blood act ivat ing method can decrease blood serum ET levels, and increase blood serum VEGF expression.Qi deficiency blood stasis is the initiating factor and fundamental disease mechanism in digital gangrene. Hence, qi replenishing blood activating method is the main method in treating this disease. Qi replenishing blood activating method is an important method in modern TCM treatment of arteriosclerotic diseases. Vessel collateral dredging stasis decoction, formulated under the therapeutic method of qi replenishing blood activating, reflects the classical TCM theory "Qi is the commander of blood, blood is the mother of qi, if qi moves then blood moves, if qi stagnates then blood stasis".The third section:observation of therapeutic effect. Therapeutic effect of Professor Pang He’s empirical formula, vessel collateral dredging stasis decoction, on digital gangrene qi deficiency blood stasis pattern was observed.60patients from the Beijing university of Chinese medicine Dong Fang hospital that were admitted between March2013to December2013were diagnosed and observed under protocols referenced from "China Society of Chinese and Western integration medicine peripheral vascular disease Committee diagnostic standards set in1995" and "Standards of diagnosis and therapeutic effect for TCM diseases and patterns"(ZY/T001.2-94). The patients admitted into our study group had been diagnosed with either qi deficiency blood stasis pattern or pattern of vessel collateral static blood obstruction.Treatment plan: basic treatment: Xue Sai Tong (Notoginseng triterpenes) injection and internal medicine treatment; Control group treatment plan: only basic treatment was administered; Chinese medicine group treatment plan: basic treatment plan plus Chinese medicine treatment vessel collateral dredging stasis decoction was used: Milkvetch root60g, Sanqi12g, medicinal Cyathula root10g, Cassia twig12g, Hirsute shiny Bugleweed herb20g, Earthworm10g)."Digital gangrene clinical verification scheme" was used as reference for therapeutic efficacy evaluation standards. Results: Therapeutic efficacy was evaluated using evaluation standards set by "Chinese National traditional Chinese medicine association blood vessel Committee". Healed:control group:3cases (10%), Chinese medicine treatment group:4cases (13.33%); significant effect:control group:12cases (40%), Chinese medicine treatment group:16cases (53.33%); effective:control group:14cases (46.67%), Chinese medicine treatment group:10cases (33.33%); non-effective:control group:1cease (3.33%).Statistically significant difference was observed between treatment scores of the control group and vessel collateral dredging stasis decoction groups for improvements in clinical symptoms such as numbness and cold. Discussion: Early diagnosis, early treatment, and use of vessel collateral dredging stasis decoction, which uses qi replenishing blood activating method as a guideline, clearly has clinical value in treatment of digital gangrene qi deficiency blood stasis pattern. |
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