Why can leeches treat cerebral thrombosis?

Sexual taste: salty; Bitter; Gender equality; Toxic meridian tropism: liver meridian effect: breaking blood and removing blood stasis; Indications: amenorrhea due to blood stasis; A lump; Usage and dosage of traumatic injury: oral administration: decoction, 3-9g; Or take pills or powder, 0.5- 1.5g each time, 3g each time. Contraindications to medication: it is forbidden for people with physical deficiency and blood deficiency, pregnant women, women during menstrual period and those with bleeding tendency. Efficacy classification: blood-activating drugs; Argument of meridian-dredging drugs: 1 Herbal decoction: leech, bitter blood, salty wins blood, Zhongjing uses scale insects and leech as soup, salty and bitter drains animal blood, so there is no principle of clouds in the classics. 2. Classic of Materia Medica: Leech is salty, bitter, flat, highly toxic, and its usage is similar to that of tabanus, so it is often used with Zhongjing Fang. Salty blood enters the blood, which tastes bitter and bitter, so it is used to treat daughters who hate blood, stagnate blood, close the moon and accumulate blood, so they have no children. Blood beast bladder, waterway impassability, blood scattered bladder gasification, waterway self-interest. Abortion with poison and good blood. 3. "Materia Medica": Leech, a medicine for expelling blood and removing blood stasis. Fang Longtan said that according to the theory of medicinal properties, this medicine can treat livestock blood, anemia and hematocele, and treat women who have no children and become dry blood. All of them are stagnant blood, blocked pulse, no monthly contact and no children. The monthly events are not in the present, but in stagnation and blood stasis, gradual fever, cough, yellow and thin blood, and exhaustion into illness. When it is adjusted to Chong Ren, it becomes pregnant and the blood disappears. Therefore, Zhongjing recipe is used to treat blood dryness, bone steaming, onychomycosis and cough. Those who enter the turtle shell in Wan Jian are treated with chronic malaria, yellow face with cold and heat, abdominal distension and fatigue; Taking Didang decoction and pills to treat typhoid fever, abdominal whiplash and egoistic urination mania belongs to animal blood syndrome. 4. Records of 100 Kinds of Materia Medica: Ordinary people are blocked by blood stasis, but Yu Nu is easy to cure. If it is blocked for a long time, it is lifeless and difficult to treat. Covering blood has nothing to do with meridians and vital qi. Take light medicine and you won't accept it. If the drug is too strong, it will hurt the invincible blood, so it is extremely difficult to treat. Leeches like the blood of cannibals best, but they are slow and powerful. If it is slow, it will produce blood without injury, but if it is good, it will be difficult to break. It is beneficial and harmless to use their strength to combat the long-standing stagnation. 5. "Classic": the Lord exorcises evil blood, blood stasis, closes the moon, breaks blood stasis, and has no children to benefit the waterway. 6. "Don't record": Abortion. 7. "Compendium of Materia Medica": People suffering from red and white virginity and carbuncle swelling, take more than ten pieces of the affected area, and take skin wrinkles and white meat. 8. "Materia Medica Yi Yan": Treating injuries and folding. Selected prescription: Didang Tang's Treatise on Febrile Diseases: Breaking Blood and Removing Blood Stasis; Didang Pill Treatise on Febrile Diseases: Breaking blood and removing blood stasis; Peach kernel pill "Sheng Hui Fang": breaking blood; Dihuang Tongjing Pill "Woman": breaking blood and removing blood stasis; Fang Jisheng: Textual research on breaking blood and removing blood stasis: from 1. Shennong's herbal classics. 2. Compendium of Shu Materia Medica: (Use leeches) Don't misuse leeches and mud leeches. Mud leech, with sharp head and thick waist, is red and not used as medicine. If eaten by mistake, it will make people look like smoke and gradually cause dryness. Pharmacological action: 1. Anticoagulant and antithrombotic effects: 0.45g/kg leech water extract has obvious inhibitory effect on ADP-induced platelet aggregation in rats after continuous gavage for 4 hours and 7 days, and its inhibitory rate increases with the increase of drug concentration, which can reduce the specific viscosity of whole blood and plasma and shorten the electrophoresis time of red blood cells; In vitro experiments, leech water extracts of 200mg/ml, 100mg/ml and 50mg/ml also have obvious inhibitory effects on platelet aggregation in healthy people. The alcohol extract of leech has stronger inhibitory effect on blood coagulation than scale insects, scale insects and peach kernels. Alcohol preparation is more effective than water preparation. 1. 1. Anticoagulant effect: Hirudin (hirudin) is a thrombin inhibitor, which is not destroyed by heat or ethanol. Each mg of hirudin contains 10 and 400 antithrombin units. 20mg hirudin can prevent 100g human blood coagulation. 1. 1. 1. The results show that hirudin is by far the strongest thrombin inhibitor in the world. It combines with thrombin to form a non-valence complex. The complex is extremely stable, and its dissociation constant is in the order of 10- 12. And the reaction speed is extremely fast. Due to the strong affinity between hirudin and thrombin, thrombin can be neutralized at a very low concentration. 1μg hirudin can neutralize 5μg thrombin, and the corresponding molar ratio is 1: 1. The anticoagulant activity of hirudin is determined by standard thrombin. The amount of hirudin that can neutralize one international unit (NIH unit) of thrombin is one anticoagulant unit (lAT-μ). 1. 1.2. Hirudin can not only prevent fibrinogen from coagulating, but also prevent thrombin from catalyzing further congestion. For example, the activation of coagulation factors ⅴ, ⅶ and ⅷ and thrombin-induced platelet reaction can be inhibited by hirudin. Its inhibition rate depends on the concentration of hirudin, and blood coagulation is delayed or completely prevented. 1. 1.3. Hirudin not only has anticoagulant effect, but also has effect on the non-blood stasis phenomenon of other cells induced by thrombin. Such as inhibiting the proliferation of fibroblasts induced by thrombin and the stimulation of endothelial cells by thrombin. 1. 1.4. Hirudin can also inhibit the action of thrombin on platelets, inhibit the combination of thrombin and platelets, inhibit the release of platelets stimulated by thrombin, and dissociate thrombin from platelets. Josenh A Jakubowski et al. synthesized the hirudin fragment of 12 peptide according to the pattern of hirudin C-terminal residue (53-64), and its anticoagulant effect was stronger than hirudin, and the partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT) were all prolonged. In the inhibition of thrombin-induced platelet activity, this fragment mainly inhibits platelet aggregation, serotonin release and TXA2 formation. Jean Marc Schlaeppi and others prepared monoclonal antibodies against hirudin, and studied the interaction between hirudin and thrombin. It was found that the binding sites of these antibodies and hirudin were all close to C-terminal residues. 1. 1.5. Hirudin is different from hirudin. The function of hirudin is to inactivate thrombin and inhibit blood coagulation, while the function of hirudin isolated from non-medicinal leeches is to directly dissolve plasminogen and fibrin. The salivary gland extract of Haemaphysalis africana was not found to contain thrombin inactivator and human plasminogen activator. The experiment also proved that Ca (2+) is not the driving factor of hirudin anticoagulation. Because hirudin has anticoagulant effect in human and pig plasma and human pure plasminogen, this discovery has certain value. First of all, like hirudin, it can be used as a tool to study coagulation mechanism. Secondly, hirudin is not sensitive to the protease inhibitor existing in plasma, which is a unique fibrinolytic enzyme known. It has ideal characteristics in dissolving thrombin preparation and has potential value in dissolving thrombus and treating some diseases caused by thrombus, such as thrombosis. 1.2. Antithrombotic effect: 1.2. 1. Hirudin can prevent thrombosis caused by bacterial endotoxin in rats and reduce the mortality of rats. 1.2.2. Fan Li et al. made an experimental study on the thrombolytic effect of hirudin, and the results showed that it had obvious inhibitory effect on experimental thrombosis (Huiyan method); It has thrombolytic effect on experimental venous thrombosis caused by lysozyme. 1.2.3. Matsuda Xiushu et al. used 70% ethanol extract of leech and other medicinal materials as experimental materials, and conducted experiments in vivo and in vitro. The results show that leech and other medicinal materials have completely different antithrombotic effects from Cortex Moutan, Cortex Cinnamomi Japonici and Radix Paeoniae Alba used for initial blood stasis, and their functions are not to prevent thrombosis, but to dissolve thrombus. 1.2.4. Hirudin is effective for all kinds of thrombosis, especially for venous thrombosis and disseminated intravascular coagulation (DIC). Appropriate amount of hirudin can inhibit carotid thrombosis in rats and rabbits, and the thrombosis is smaller than that in the control group. Hirudin can completely inhibit carotid and coronary thrombosis caused by vascular wall injury. It can effectively inhibit microthrombosis in rats and weaned piglets, alleviate the changes of coagulation system caused by thrombin or endotoxin, and reduce fibrin deposition. 1.2.5. For different experimental models, the effective dose and blood concentration of antithrombotic drugs are different. Experiments were conducted in rats to compare the effective concentration of hirudin in the treatment of various thrombosis. The plasma concentration of hirudin required for venous thrombosis and disseminated intravascular coagulation (DIC) is the lowest, and both are lower than heparin. The blood concentration of hirudin in the treatment of venous thrombosis is 1/20 of heparin, while the blood concentration of DIC is only 1/50 of heparin. Because in the process of venous thrombosis, the main plasma coagulation factors are activated, leading to the formation of thrombin, and hirudin is the strongest thrombin inhibitor. The treatment of arterial thrombosis requires higher plasma concentration. B. Kaiser and F. Markwardt found that hirudin was injected intravenously at a rate of 40AT-μ/kg in rats. Min and plasma concentration of 4.3 AT-μ/ml completely inhibited venous thrombosis. However, in order to completely inhibit arterial thrombosis, it is necessary to administer it at a dose of 200 AT-μ/kg.min for 60 minutes. The inhibitory effect on arterial thrombosis is 5 times higher than that of venous thrombosis, and the dose of hirudin is 5 times higher. Compared with heparin, the concentration of hirudin in inhibiting thrombosis is far less than that in causing bleeding. At the blood concentration that completely inhibits arterial thrombosis, it only leads to a prolonged bleeding time of 50-60%, while heparin has serious bleeding side effects. 1.2.6. Compared with heparin, hirudin has a significant advantage, that is, it does not increase the dosage of antithrombin-Ⅲ (AT-Ⅲ). Both heparin and hirudin can inhibit the effect of thrombin on fibrinogen and platelets, but hirudin has nothing to do with cofactors. In the course of DIC, at-ⅲ will decrease, thus reducing the therapeutic effect of heparin on DIC. When the concentration of AT-gd in plasma is lower than 70-80% of the normal value, there is a risk of thrombosis. 2. Hypolipidemic effect: 32 healthy rabbits, weighing 2.0-2.5kg, regardless of sex. All rabbits were randomly divided into three groups, namely, modeling level (n = 9), prevention group (n=8) and treatment group (n= 1 1), and each rabbit was fed 0.8g of cholesterol every day. Four rabbits died of diarrhea. In the prevention group, each rabbit was given leech (naturally dried) powder of 65438±0g every day at the beginning of modeling, and in the treatment group, leech powder was given after modeling. The method is as above. The model group received no other drugs except cholesterol 0.8g/ day, and continued to take it for 6 weeks as a control. Blood was taken from the external femoral vein before and after modeling and after treatment, and serum total cholesterol (TC), triglyceride (TG), 6- keto PGF 1α, tx B2 1 time were measured respectively. After 6 weeks of treatment, all rabbits were killed by air embolism through ear vein and dissected immediately. Take out the whole aorta from the starting point of aorta to the common iliac artery and peel off the adventitia. After longitudinal incision, it was fixed in formalin and stained with Sudan ⅲ. The percentage of atherosclerotic (AS) plaque area of each aorta to the total area of aorta or coronary artery was calculated by nine squares method, and then paraffin sections were made and examined by he staining. The results are as follows: (1) Preventive effect: Leech has a good inhibitory effect on the increase of TC and TG; After leech administration, the value of 6- keto -PGF 1α increased, while TXB2 decreased, and both values remained in the normal range. The atherosclerotic lesions in hyperlipemia rabbit model group and leech group were significantly different (P < 0.0 1). Efficacy: After leech powder treatment, TC and TG decreased significantly; 6- keto -PGF 1α increased significantly, while TXB2 decreased significantly. Compared with the treatment group, the pathological changes of atherosclerosis in the model group were significantly different (P