CN103041368B - Application of phycocyanin in preparation of drug for preventing and treating embryotoxicity caused by organophosphorus pesticide - Google Patents
Application of phycocyanin in preparation of drug for preventing and treating embryotoxicity caused by organophosphorus pesticide Download PDFInfo
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- CN103041368B CN103041368B CN201310018431.6A CN201310018431A CN103041368B CN 103041368 B CN103041368 B CN 103041368B CN 201310018431 A CN201310018431 A CN 201310018431A CN 103041368 B CN103041368 B CN 103041368B
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Abstract
The invention relates to a new medical use of phycocyanin, namely for preventing and treating embryotoxicity effect caused by an organophosphorus pesticide and restraining the effects of reduction of embryo survival rate, increment of dead embryo rate or embryo absorption rate, and reduction of placenta weight caused by organophosphorus pesticide. Proved by a pharmacological test, the phycocyanin disclosed by the invention can restrain reduction of living embryo number and living embryo rate of pregnant mice, increment of dead embryo rate and embryo absorption rate and reduction of weight, body length, tail length and placenta weight of the living embryo mice caused by organophosphorus pesticide (such as azodrin and phoxim). The phycocyanin can restrain embryotoxicity caused by the organophosphorus pesticide and has good dose dependent. The phycocyanin has good inhibition effect for embryotoxicity caused by the organophosphorus pesticide, can be used for preparing drugs for preventing and treating embryotoxicity caused by the organophosphorus pesticide, and further can be used for preparing drugs for preventing and treating diseases induced by embryotoxicity caused by the organophosphorus pesticide.
Description
Technical field
The present invention relates to relate to the application of phycocyanin, be specifically related to phycocyanin in preparation prevention and treat because of the application in the medicine of caused by organophosphorus pesticide fetal toxicity disease.
Background technology
Organophosphorus pesticide (OPs) is that a class is efficient, the pesticide of low-residual, the wide spectrum pesticide that has become that China Today uses.Distinctions won on the battlefield have been made in volume increase that the use of organophosphorus pesticide is agriculture, woods, fishery good harvest, but along with being widely used of organophosphorus pesticide, its residual phenomena in the foods such as vegetable and fruit is also comparatively general.Although it is poisoning that most people has been noted preventing in organophosphorus pesticide acute, long-term, low dosage, the impact of Chronic exposure on human health, the especially anemia of pregnant woman of organophosphorus pesticide expose the impact on offspring, also do not cause people's enough attention.Epidemiological study is both at home and abroad found, for a long time, suffer the area of organophosphorus pesticide pollution or the workman of insecticide factory, menstrual cycle of female changes, miscarriage increases, fetal intrauterine growth retardation, ovarian cancer and breast cancer incidence rising (Arbuckle TE, Lin Z, Mery LS, et al.An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an ontario farm population.Environ Health Perspect, 2001, 109:851-857.).We and multidigit scholar's research are both at home and abroad found, organophosphorus pesticide has fetal toxicity, organophosphorus pesticide exposes, can cause pregnant mouse, body weight increases and reduces, the tire number of living reduces, stillborn fetus and absorption tire number increase, young for birth weight decline, hypoevolutism, deformity (Farag AT, Karkour TA, El-Okazy A.Developmental toxicity of orally administered technical dimethoate in rats.Birth Defects Res B Dev Reprod Toxicol, 2006,77:40-46.).Therefore inquire into the fetal toxicity mechanism of action of organophosphorus pesticide, find limited intervention medicine, healthy most important for protection China people.
Phycocyanin (phycocyanin) is a kind of phycocyanobilin protein extracting from spirulina, and the content in spirulina, up to 10%～20%, is one of rare chromoprotein of occurring in nature.Phycocyanin is not only a kind of fabulous natural food colour, and itself is a kind of nutritious protein, and its aminoacid forms complete, and essential amino acids content is high.Phycocyanin has been proved to be and can have suppressed cancer cell expansion, can make antineoplastic adjuvant therapy medicaments, immunity that can enhancing body in order to the auxiliary treatment of chemotherapy; Phycocyanin can help to regulate, the needed multiple important enzyme of synthesized human metabolism, promotes the regeneration of human body cell, regulates human immune system, strengthens function of immune system, improves the resistance of human body to disease; Phycocyanin also can be removed interior free yl, promotes cytoactive, improves ovarian function, promotes human body synthetic elastin fast; Phycocyanin also has the erythrocyte of stimulation colony formation, the effect of similar erythropoietin, and the effect that can adjust leukocyte and improve lymphocyte activity, increases physical ability, promotes erythrocyte to increase, enhancing development; Phycocyanin also has radioprotective, antiallergic, resisting fatigue, antiviral, antiinflammatory and neuroprotective.Phycocyanin is without any side effects, can long-term taking.
Summary of the invention
The object of the present invention is to provide the new medicine use of phycocyanin aspect preparation control caused by organophosphorus pesticide body injury.
Specifically, the present invention relates to the application of phycocyanin in the medicine of preparation control caused by organophosphorus pesticide fetal toxicity.
In addition, also relate to the application in the medicine of the disease that phycocyanin brings out because of caused by organophosphorus pesticide fetal toxicity in preparation prevention and treatment.
Wherein said disease is the fetal toxicity disease because of caused by organophosphorus pesticide, mainly comprises: stillborn fetus, embryo's deformity, embryo growth retardation, birth defect, hysteropathy, placenta disease etc.
Organophosphorus pesticide of the present invention is the conventional organophosphorus pesticides such as Azodrin, phoxim, paraoxon, triazophos.
Medicine refers to and take phycocyanin as main active under the present invention, and acceptable preparation in the medical treatment made from pharmaceutically suitable carrier, as tablet, pill or capsule etc.
The present invention finds by animal experiment study: take the effect that phycocyanin can reach the fetal toxicity of control caused by organophosphorus pesticide, play and suppress because of embryo's tire rate decline alive, embryo's still birth rate of caused by organophosphorus pesticide or the series of problems that absorption tire rate raises, placental weight declines.The treatment effective dose of phycocyanin, should determine according to the age of therapist, health, contact organophosphorus pesticide amount etc.
Phycocyanin of the present invention is one of main active of spirulina, it has immunoregulatory activity, can play the effects such as antitumor, antioxidation, antiviral, antiinflammatory, radioprotective, resisting fatigue, antiallergic, and not yet find that at present it has any toxic and side effects.Phycocyanin can obtain by commercially available, also can extract acquisition by several different methods, and extracting method is ripe.
It is representative that the inventor be take the malicious organophosphorus pesticide Azodrin of height and low toxicity organophosphorus pesticide phoxim, studied the fetal toxicity effect of organophosphorus pesticide, the fetal toxicity effect that finds that there is machine phosphorus insecticide is mainly to cause that pregnant Mus absorbs tire rate and still birth rate raises, every nest is lived, and tire number reduces; Tire Mus body weight alive, height, tail length and placental weight decline, thereby cause as a series of diseases such as fetal birth deformity, miscarriage, stillborn fetus, embryo growth retardation, birth defects.
The fetal toxicity effect of organophosphorus pesticide to mice that the present invention has passed through animal experimental observation, and the inhibitory action of phycocyanin to organophosphorus pesticide fetal toxicity.Find after deliberation, phycocyanin can suppress the pregnant Mus tire number alive of (as Azodrin and phoxim) caused by organophosphorus pesticide, body weight, the body of live tire rate decline and still birth rate, the rising of absorption tire rate and tire Mus are long, tail is long and the decline of placental weight, phycocyanin can suppress the fetal toxicity of organophosphorus pesticide, has good dose dependent.
Beneficial effect of the present invention is:
1. the invention provides the positive evidence of organophosphorus pesticide to body fetal toxicity effect, and find effective intervention medicine with this.
2. the invention provides the new medical use of phycocyanin, its fetal toxicity that organophosphorus pesticide is caused has good inhibition and protective effect.Pregnant Mus body weight increase minimizing, absorption tire rate and still birth rate that phycocyanin can suppress due to organophosphorus pesticide (as Azodrin) raise, and the tire number minimizing alive of every nest, tire Mus body weight alive, height, tail length and placental weight decline, and have good dose dependent.
3. the present invention has profound significance to the people of Long Term Contact organophosphorus pesticide especially anemia of pregnant woman, can play protection anemia of pregnant woman and filial generation thereof healthy, improve the quality of living, reduce the effects such as sterility and infertility, prenatal and postnatal care, life-saving.
The specific embodiment
By test example, further set forth below new medical use and the beneficial effect thereof of phycocyanin in the present invention, but be not used for limiting the scope of the invention.
Test example 1: the experimental study of fetal toxicity due to phycocyanin inhibition Azodrin
1 materials and methods
1.1 material
Azodrin (40% preparation, Qingdao insecticide factory), phycocyanin (Chinese Marine University is so kind as to give).
1.2 laboratory animals and grouping
Select 120 of healthy SPF level sexual maturity kunming mices, body weight is between (25 ± 2) g, female: hero is 2: 1, purchased from Xinxiang College of Medical Science's zoopery center.Adaptability is raised 7d, room temperature (25 ± 2) ℃, humidity 50%-55%.
By mice by female: hero is to mate copulation at 2: 1, checks that female Mus has depletion of YIN bolt morning next day, and the female Mus of depletion of YIN bolt is got vaginal secretions with the cotton swab that soaks normal saline and is applied on the microscope slide that contains a normal saline, under low power lens, checks and has or not sperm.Be decided to be the 0th day pregnancy period the same day of finding cloudy bolt or sperm.The female Mus of insemination is divided into 6 groups at random, 15 every group.Be respectively dosage protection group (E) in Normal group (A), phycocyanin matched group (B), Azodrin matched group (C), phycocyanin low dosage protection group (D), phycocyanin.Wherein not administration of matched group (A); give distilled water; phycocyanin matched group (B) give phycocyanin 100mg/kg; Azodrin matched group (C) give 0.20mg/kg; phycocyanin low dosage protection group (D) gives phycocyanin 50mg/kg+ Azodrin 0.20mg/kg; in phycocyanin, dosage protection group (E) gives phycocyanin 100mg/kg+ Azodrin 0.20mg/kg, and phycocyanin high dose protection group (F) gives phycocyanin 200mg/kg+ Azodrin 0.20mg/kg.And guaranteeing sufficient drinking-water and supply of forage, insemination Mus was weighed the same day.In the pregnancy period, adopt gavage mode to contaminate, poisoning dosage is 10ml/kg, every day 1 time.
1.3 statistical method
Adopt SPSS10.0 software to carry out statistical analysis.Measurement data experimental data all represents with x ± s, relatively adopts homogeneity test of variance and one factor analysis of variance (One Way ANOVA) between many groups.While comparing between two between further organizing, if when variance is neat, adopt SNK check; If during heterogeneity of variance, adopt Games-Howell check.Enumeration data experimental data all represents with rate, relatively adopts between two chi-square criterion between group.The P < 0.05 of take has statistical significance as difference.
2 methods and result
In the 20th day pregnancy period, put to death pregnant Mus, cut taking-up uterus, abdominal cavity open, record uterus weight, tire number alive, stillborn fetus number (containing early stage and late fetal death) and absorb tire number.Get tire Mus and Placenta Hominis, claim live tire Mus body weight and Placental Weight, measurement body is long, tail is long.Result as shown in Tables 1 and 2.
The protective effect (n=15) that table 1 phycocyanin raises to pregnant Mus uterus weight due to Azodrin and the tire number of living, live tire rate decline and still birth rate, absorption tire rate
Note: compare with A group: * P < 0.05, compares with C group: Δ P < 0.05.
Table 1 demonstration, compares with Normal group (A), and Azodrin matched group (C) tire number alive and the tire rate of living all decline, and still birth rate and absorption tire rate all raise, and difference has statistical significance (P < 0.05).Phycocyanin protection group can suppress pregnant Mus tire number alive, tire rate decline alive and still birth rate, the rising of absorption tire rate that Azodrin contamination causes; the most remarkable with phycocyanin high dose protection group (F) effect; phycocyanin high dose protection group (F) tire number alive, the tire rate of living and still birth rate, absorption tire rate; compare with Azodrin matched group (C) that there were significant differences (P < 0.05); compare with Normal group (A), there is no significant difference (P > 0.05).
Table 2 phycocyanin is to tire Mus body weight due to Azodrin, body is long, tail is long, placental weight declines protective effect (n=15)
Note: compare with A group: * P < 0.05, compares with C group: Δ P < 0.05.
Table 2 is visible, compares with Normal group (A), and the body weight of Azodrin phosphorus matched group (C) tire Mus, body length, tail length and placental weight all decline, and difference has statistical significance (P < 0.05).Phycocyanin protection group can suppress that body weight, the body of the tire Mus that Azodrin contamination causes is long, tail is long and placental weight declines; the most remarkable with phycocyanin high dose protection group (F) effect; the body weight of phycocyanin high dose protection group (F) tire Mus, body length, tail length and placental weight; compare with Azodrin matched group (C) that there were significant differences (P < 0.05); compare with Normal group (A), there is no significant difference (P > 0.05).
Test example 2: the experimental study of fetal toxicity due to phycocyanin inhibition phoxim
1 materials and methods
1.1 material
Phoxim (40% cream, Shandong Dongtai Agrochemical Co., Ltd), phycocyanin (Chinese Marine University is so kind as to give Life Sciences).
1.2 laboratory animals and grouping
Select 120 of healthy SPF level sexual maturity kunming mices, body weight is between (25 ± 2) g, female: hero is 2: 1, purchased from Xinxiang College of Medical Science's zoopery center.Adaptability is raised 7d, room temperature (25 ± 2) ℃, humidity 50%-55%.
By mice by female: hero is to mate copulation at 2: 1, checks that female Mus has depletion of YIN bolt morning next day, and the female Mus of depletion of YIN bolt is got vaginal secretions with the cotton swab that soaks normal saline and is applied on the microscope slide that contains a normal saline, under low power lens, checks and has or not sperm.Be decided to be the 0th day pregnancy period the same day of finding cloudy bolt or sperm.The female Mus of insemination is divided into 6 groups at random, 15 every group.Be respectively dosage protection group (E) in Normal group (A), phycocyanin matched group (B), phoxim matched group (C), phycocyanin low dosage protection group (D), phycocyanin.Wherein not administration of matched group (A); give distilled water; phycocyanin matched group (B) give phycocyanin 100mg/kg; phoxim matched group (C) give 20mg/kg; phycocyanin low dosage protection group (D) gives phycocyanin 50mg/kg+ phoxim 20mg/kg; in phycocyanin, dosage protection group (E) gives phycocyanin 100mg/kg+ phoxim 20mg/kg, and phycocyanin high dose protection group (F) gives phycocyanin 200mg/kg+ phoxim 20mg/kg.And guaranteeing sufficient drinking-water and supply of forage, insemination Mus was weighed the same day.In the pregnancy period, adopt gavage mode to contaminate, poisoning dosage is 10ml/kg, every day 1 time.
1.3 statistical method
Adopt SPSS10.0 software to carry out statistical analysis.Measurement data experimental data all represents with x ± s, relatively adopts homogeneity test of variance and one factor analysis of variance (One WayANOVA) between many groups.While comparing between two between further organizing, if when variance is neat, adopt SNK check; If during heterogeneity of variance, adopt Games-Howell check.Enumeration data experimental data all represents with rate, relatively adopts between two chi-square criterion between group.The P < 0.05 of take has statistical significance as difference.
2 methods and result
In the 20th day pregnancy period, put to death pregnant Mus, cut taking-up uterus, abdominal cavity open, record uterus weight, tire number alive, stillborn fetus number (containing early stage and late fetal death) and absorb tire number.Get tire Mus and Placenta Hominis, claim live tire Mus body weight and Placental Weight, measurement body is long, tail is long.Result as shown in Table 3 and Table 4.
Table 3 phycocyanin is to pregnant Mus uterus weight due to phoxim and the tire number of living, live tire rate decline and still birth rate, absorption tire rate height protective effect (n=15)
Note: compare with A group: * P < 0.05, compares with C group: Δ P < 0.05.
Table 3 demonstration, compares with Normal group (A), and phoxim matched group (C) tire number alive and the tire rate of living all decline, and still birth rate and absorption tire rate all raise, and difference has statistical significance (P < 0.05).Phycocyanin protection group can suppress pregnant Mus tire number alive, tire rate decline alive and still birth rate, the rising of absorption tire rate that phoxim contamination causes; the most remarkable with phycocyanin high dose protection group (F) effect; phycocyanin high dose protection group (F) tire number alive, the tire rate of living and still birth rate, absorption tire rate; compare with phoxim matched group (C) that there were significant differences (P < 0.05); compare with Normal group (A), there is no significant difference (P > 0.05).
Table 4 phycocyanin is to tire Mus body weight due to phoxim, body is long, tail is long, placental weight declines protective effect (n=15)
Note: compare with A group: * P < 0.05, compares with C group: Δ P < 0.05.
Table 4 is visible, compares with Normal group (A), and the body weight of phoxim matched group (C) tire Mus, body length, tail length and placental weight all decline, and difference has statistical significance (P < 0.05).Phycocyanin protection group can suppress that body weight, the body of the tire Mus that phoxim contamination causes is long, tail is long and placental weight declines; the most remarkable with phycocyanin high dose protection group (F) effect; the body weight of phycocyanin high dose protection group (F) tire Mus, body length, tail length and placental weight; compare with phoxim matched group (C) that there were significant differences (P < 0.05); compare with Normal group (A), there is no significant difference (P > 0.05).
From above each experimental example, can find out, phycocyanin can suppress the pregnant Mus tire number alive of (as Azodrin and phoxim) caused by organophosphorus pesticide, body weight, the body of live tire rate decline and still birth rate, the rising of absorption tire rate and tire Mus are long, tail is long and the decline of placental weight, phycocyanin can suppress the fetal toxicity of organophosphorus pesticide, has good dose dependent.To caused by organophosphorus pesticide, fetal toxicity has good inhibition and protective effect to phycocyanin; the medicine that can be used for the fetal toxicity of preparation control caused by organophosphorus pesticide, also can be used for the medicine that preparation prevented and treated the disease of bringing out because of caused by organophosphorus pesticide fetal toxicity.
Although, above by general explanation, specific embodiments and test example, the present invention is described in detail, but on basis of the present invention, those of ordinary skill in the field can to some modifications of do and improvement, this will be apparent to those skilled in the art.Therefore without departing from theon the basis of the spirit of the present invention, these modifications and the improvement made, all belong to the scope of protection of present invention.
Claims (2)
1. the application of phycocyanin in the medicine of the fetal toxicity of preparation prevention caused by organophosphorus pesticide, is characterized in that tire number alives, live tire rate decline and still birth rate that described phycocyanin can suppress organophosphorus pesticide and cause, absorption tire rate raises and the decline of embryo's body weight, body length and weight.
2. application according to claim 1, is characterized in that described organophosphorus pesticide is Azodrin, phoxim, paraoxon, four kinds of conventional organophosphorus pesticides of triazophos.
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| WO2006036686A2 (en) * | 2004-09-24 | 2006-04-06 | University Of Maryland, Baltimore | Method of treating organophosphorous poisoning |
| CN101899102B (en) * | 2010-07-12 | 2013-05-08 | 华南理工大学 | Method for separating high purity phycocyanin from spirulina |
| CN101942014B (en) * | 2010-08-23 | 2013-07-24 | 中国科学院烟台海岸带研究所 | Food grade phycocyanin and preparation method thereof |
| CN102579477B (en) * | 2012-04-01 | 2013-04-03 | 新乡医学院 | Application of spirulina phatensis polysaccharide in preparing medicament for preventing and treating embryotoxicity caused by organophosphorus pesticide |
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