| Objective: The toxic effects,doses and models of aconite on embryos were studied by different models and doses.The toxicological and pharmacological effects of different extracts of Aconite on the model rats were studied.Methods: 1.Establishment of a rat model of pregnancy-deficient abdominal pain: The cold-drug drug gypsum and Zhimu(3:4)100% decoction were administered on the 7th day of pregnancy.The rats were intragastrically injected with 3% glacial acetic acid for 3 days/kg,and the rats were examined for body weight,rectal temperature and writhing.The incubation period and the number of writhing,thyroid hormone,serum sex hormone and gonadotropin levels,copy the TCM syndrome model of pregnancy deficiency and abdominal pain.2.Acute toxicity test of aconite in rats with abdominal pain and abdominal pain: According to the pre-test,different doses were given.One-time intragastric cold and abdominal pain rats were intragastrically administered within 24 hours.The lethal dose(LD50)was measured and the toxicity was observed.3.Toxic-effect test of aconite on rats with abdominal pain and abdominal pain: Rats were intragastrically administrated with different doses of 0.38,0.75,1.50,1.86g/kg,2.0/kg and 3.71g/kg for 7 days in pregnant rats from 7 to 20 days.The body weight,rectal temperature,writhing reaction latency and number of writhing were measured.Then dissect the rats,observe the changes of the organs and the development of the fetuses in the pregnant rats;determine the number of WBC,RBC,HGB and PLT in the peripheral blood;measure the blood biochemical indicators,the levels of sex hormones and gonadotropins,and the triiodothyronine(T3),tetraiodothyronine(T4)content.The placenta and right ovarian organ coefficient were calculated and the contents of MDA,SOD and GSH-Px in the placenta were detected,and pathological examination was performed on the ovary and placenta.4.Toxic effect test of salt aconite on normal pregnant rats 4.Toxic-effect test of aconite on normal pregnant rats Normal pregnant rats were intragastrically administrated with normal doses of 0.38,0.75,1.50,1.86,2.0,3.71 g/kg for 7 days in pregnant rats for 7-15 days.The body weight and rectal temperature of the rats were measured,and the writhing reaction was the incubation period and the number of writhing.The changes of organs and fetal rats were observed.The hematology and blood biochemical indexes were measured.The levels of sex hormones and gonadotropins in each group were measured by ELISA.The placenta and ovary were weighed and the organ coefficient was calculated.Placental homogenate was measured by kit for determination of MDA,SOD,GSH-Px,and pathological examination of ovary and placenta.5.Cell screening test for embryotoxic substances Rat ovarian granulosa cells were cultured in vitro,and the effects of different components and different components of aconite on the viability of ovarian granulosa cells in normal rats were detected by MTT assay..Result: 1.The performance of the model of pregnancy-deficient abdominal pain: compared with the normal rat group,the model group began to have diarrhea on the 2nd day after gavage,with hair standing,fatigue,less movement,poor spirit,and significantly lower body weight and anus temperature(P ?0.05 or P?0.01),but no blood or other abnormalities in the vagina flow out;the incubation period of writhing reaction induced by glacial acetic acid was significantly shortened on the 21 st day of pregnancy(P?0.05),and the number of writhing was significantly increased(P?0.01).It can be seen that the number of pregnant fetuses in each pregnant mouse is between 10 and 20,and the development of fetal rats(number of embryos,number of live fetuses,ratio of live fetuses,number of terats,number of fetuses,coefficient of embryos)and normal There was no significant difference in the group comparison.The above performance is consistent with the symptoms of pregnancy-induced cold and abdominal pain,so the model is considered successful.2.Acute toxicity test results of aconite in rats with abdominal cold and abdominal pain.The LD50 and 95% confidence interval of aconite in rats with abdominal cold pain were 7.43(6.82~8.12)g/kg.The toxicity performances were as follows: Light,closed,less active,slow-responding,shallow breathing,severe mental dysfunction,intermittent mouth breathing,perioral salivation or foaming at the mouth,large and urinary incontinence,followed by quiet death within 2 to 24 hours,or Gradually returned to normal.3.Toxic-effect test results of aconite on rats with abdominal cold and abdominal pain: Compared with the normal group,the rats in the model group were generally in poor condition,and the body weight decreased significantly from the 5th day after modeling(P?0.05).On the 3rd day,the decrease was significant(P?0.01);the latency of writhing reaction was shortened and the number of writhing was increased(P?0.05 or P?0.01).The number of embryos,the number of live births,the number of terats,There was no significant difference between the number of absorbed fetuses and the index of embryonic organs;the levels of serum T3,T4,E2,PROG decreased significantly and the contents of T and FSH increased significantly(P?0.05,and LH also increased;The visceral coefficient of ovary and placenta was not abnormal,but the activity of SOD in placenta was significantly increased(P?0.05),the activity of GSH-Px and MDA content increased.HE staining showed that the trophoblast cells of placental tissue in model group decreased.Structural disorder,sinusoidal dilatation and hyperemia,interstitial loose edema,focal inflammatory cell infiltration in the decidua and labyrinth,no other histopathological changes in the ovary;peripheral blood RBC,HGB decreased significantly and WBC increased significantly(P?0.05),the number of PLT is reduced Trends;CHOL and HDL-C levels were significantly increased(P?0.05),but had no significant effect on liver and kidney function related indicators.Compared with the model rats,the changes of each index were as follows: the general state of the rats in different doses of aconite was similar to that of the model group,and the weight of the rats in the 0.38g/kg group was significantly higher than that in the model group(P?0.05),and 3.71g/kg.The body weight of the group was significantly lower than that of the normal group(P?0.05),which was similar to the model group.On the 3rd day of administration,the anus temperature of the rats in the 0.38g/kg group increased significantly and decreased significantly in the 1.86 and 3.71g/kg groups(P?0.05).There was no significant difference between the anus temperature and the model group in the drug group of the 7th day,but the anal temperature of the dose group of 1.50g/kg and below increased,and the anus temperature of 1.86g/kg and above decreased.The rats of various doses of aconite The number of writhings decreased,among which 0.38,0.75,1.50g/kg group had significant difference(P?0.05),and each dose except 3.71g/kg had a tendency to prolong the writhing latency.The number of embryos,the number of live fetuses,and the proportion of live fetuses in the aconite group were similar.From the numerical value,the number of embryos in the aconite 0.75g/kg group and the proportion of live fetuses were the highest,and the number of terats and the number of fetuses in the group of 3.71g/kg.Maximal;there was no significant change in the organ coefficient and placental organ coefficient of each group.The right ovarian coefficient of the 1.50g/kg group was lower than that of the model group(P?0.05).The histopathological examination results of ovarian and placental HE staining The results showed that the histopathological changes of placenta in the 0.38g/kg group were not significantly improved,and the other groups improved the reduction of placental tissue trophoblast cells and interstitial loosening,and the degree of infiltration of decidual inflammatory cells was reduced;0.75,1.50,1.86g/kg group with the increase of dose,the stronger the degree of improvement,showing a significant "quantity-effect" correlation,of which 1.86 g / kg group placenta is normal,no other histopathological changes;2.00,3.71 g In the /kg group,the placental trophoblast was normal,and the degree of diffuse inflammatory cell infiltration in the decidua was aggravated with the increase of the dose;the cortex and medulla of each group had multiple follicles at different developmental stages in the cortex,and the medulla was rich.Containing blood vessels,no other histopathology Learn to change.The SOD in the placenta tissues of the aconite group was significantly decreased,and the GSH-Px activity in the aconite 0.75,1.50,and 1.86g/kg groups was also significantly decreased (P?0.05),and the GSH-Px activity was lower than that in the normal group.In terms of serum hormones,the aconite group had no significant effect on serum T3 and T4;E2 in aconite 1.50g/kg group was significantly increased(P?0.05),and T level was significantly lower in 0.38 and 2.00g/kg group(P?0.05).There was an increase in the trend of PROG in each group;except for the aconite 0.38 g/kg group,the other groups had an increasing trend of PRL content,and had no significant effect on FSH and LH,and the values of the two indicators in the 3.71 g/kg group were The model group is the closest.Peripheral blood routine and blood biochemistry,the dose of aconite decreased the number of WBC and increased RBC,HGB,PLT,but no statistical significance,and did not reach the normal level;aconite group can significantly reduce BUN content The A/G ratio in the 0.75g/kg group and the DBIL content in the 0.38g/kg group were significantly lower(P?0.05).Crea,UA,GLU,TP,GLO,CHOL,TG,HDL-C,LDL-C and so on are similar to the model group,and there is no significant difference.4.Toxic-effect test results of aconite in normal pregnant rats: The normal group of pregnant rats in normal state during the test period,the body weight gradually increased,and the embryos were normal after the end of the experiment.Compared with the normal group,the rats in each dose group of Aconite were generally in normal condition,and the body weight and anus temperature were not significantly different from those in the normal group.The necropsy showed that the number of embryos and the number of live fetuses in each dose group were similar to those in the normal group.The proportion of live fetus was the lowest in 2.00 g/kg group,and the number of fetuses in this group was also the highest.The number of malformed fetuses was 3.71 g/kg.The group was the most,but the embryonic organ coefficients of all the drug-administered groups were significantly decreased(P?0.05).There was no significant change in the right nest coefficient of each group,but the placental organ coefficient of the 3.71g/kg group was significantly increased(P?0.05).Histopathological examination showed that the placenta tissues in the 0.38,0.75,and 1.50 g/kg groups were normal,and no other histopathological changes were observed.In the 1.86,2.00,and 3.71 g/kg groups,the degree of infiltration of the placental tissue decidual inflammatory cells was increased with the dose.The aggravation of SOD,GSH-Px activity and MDA in placental homogenate was significantly increased in each group of aconite,and the increase of SOD in 0.75,1.50,2.00g/kg group was statistically significant(P?0.05)..In terms of hormones in the body,Aconite 2.00g/kg significantly increased E2 level(P?0.05),1.86,2.00,3.71g/kg group significantly decreased PROG level(P?0.05),and other groups also reduced PROG trend.The level of T decreased.The levels of gonadotropin LH,FSH and PRL increased in each group.The effect of 2.00g/kg on LH and the increase of FSH on 0.75g/kg and above were statistically significant.Significance(P?0.05).In hematology and blood biochemistry,the two doses of 2.00 and 3.71g/kg could significantly increase the levels of RBC,HGB and PLT in peripheral blood,and the latter could significantly increase the number of WBC(P?0.05).The content of Crea and UA increased,and the increase of UA in the 0.38 and 0.75g/kg groups was statistically significant(P?0.05).The ALT level could be increased in each group,and the dose groups of 0.75,1.86 and above were compared with the normal group.Statistically significant(P ? 0.05);TP and GLO levels were significantly increased in each group(P?0.05),but had no significant effect on A/G ratio.All doses increased CHOL levels,and 0.38,1.86,2.00 In the 3.71g/kg group,the TG content was significantly increased,and the HDL-C levels of 0.75,1.86,2.00 aconite g/kg were also significantly increased(P?0.05).Conclusion: 1.In this study,a model of pregnancy-induced cold and abdominal pain was prepared on pregnant rats by gypsum-Kingshui decoction and glacial acetic acidinduced writhing method.The symptoms of chills and pain were simulated and guaranteed.The pregnancy persists during the experiment,so it is a syndrome model that can be used in the pharmacological research of traditional Chinese medicine.2.Aconite has different effects on the deficiency and abdominal pain of rats in different doses,and the protective effect is 1.50g/kg and below.It can improve the quality of the fetal embryo by regulating the sex hormone and thyroid hormone in the body.1.86g/kg and above are toxic to rats with abdominal pain and abdominal pain,which can cause hormonal disorders and are toxic to pregnant mice and embryos.3.The toxicity of aconite to normal pregnant rats is 1.86g/kg and above,which not only affects the hormone level but also abnormally changes the placental tissue morphology.The toxicity to pregnant mice and embryos is significantly lower than that of rats with abdominal cold and abdominal pain.Toxicity.4.This study found that aconite can cause dyslipidemia in pregnant rats. |
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