Study On Reproductive Toxicity Of Rhubarb In Femal Rats Based On The Dosage And Time

Rhubarb is now widely used in some Chinese patent drugs. In addition toroutine clinical application. Rhubarb are used to alleviate the hyperlipidemiaand eliminate toxin. Now there are many young women began to extensive useof diet pills for along time. Lead to long-term use of non therapeutic purposes,significantly increased the adverse reaction of the incidence. Some researchesshowed that Rhubarb lead to injury of testosterone secrtion of Leydig cells.Therefore, to observe the effects that Rhubarb had on the adult femal rats andyoung femal rats based on the indexes including LH, FSH, E2, bax, bcl-2andso on in this paper. And observe the effect of the RWE, RDA10min,RDA30min on the reproductive function of the young femal rats. At the sametime analysed the relations between the toxicity and solution preparationmethod, and for further analysis of its reproductive toxicity component to lay afoundation.Part1: the effect of the rhubarb on the reproductive function of the adultfemal ratsObjective: To observe the effect on the adult femal rats that the aqueousextract of Rhubarb had based on the time and dosage.Methods: To separate908-week wistar femal rats into nine groupsincluding NC group, test groups (Administrating rhubarb1.0g.kg-1,2.0g.kg-130d,40d,50d,60d, respectively), ten in each group. To weight the ovary anduterus observe. Calculate the index of ovary and uterus and observe thechange of in ovary and uterus, the different indexes includinghistopathological examination E2, LH, FSH, bcl-2, bax through HE,Elisa andimmunohistochemistry respectively. Results:1.The effect on the index of the ovary and uterusThe uterus index in rat is lower than NC when administered1.0g.kg-1for60d and2.0g.kg-1for40d，50d，60d respectively(P＜0.05orP＜0.01); Theovary index in rat is lower than NC when administered1.0g.kg-1for60d and2.0g.kg-1for30d,40d,50d,60d respectively (P＜0.05orP＜0.01). Thecomparison of the groups when administered different dosages for the sametime: It showed that the indexes of the ovary and uterus in the high-dosagegroup were lower than the low-dosage one when administered the Rhubarb for50d,60d, respectively (P＜0.05). The comparison of the groups whenadministered the same dosage for different time: The indexes of ovary anduterus indicated a lower level when administered1.0g.kg-1for60d than30d(P＜0.05; the indexes of ovary and uterus figure out a lower level whenadministered2.0g.kg-1for50d,60d than30d,40d(P＜0.05.2.The effect on the levels of LH、FSH、E2in the serumCompared with NC group, the level of E2was lower while that ofLH,FSH were higher when administered2.0g.kg-1for50d，60d(P＜0.05orP＜0.01). The comparison of the groups when administered different dosagesfor the same time: It showed that the levels of E2was low while that of LHand FSH were high when administered2.0g.kg-1for50d，60d compared with1.0g.kg-1(P＜0.05). The comparison of the groups when administered thesame dosage for different time: The level of E2decreased while that of LH,FSH increased when administered1.0g.kg-1for60d than30d (P＜0.05); Itshowed a higher level of E2and a lower level of LH, FSH when administered2.0g.kg-1for50d,60d compared with for30d,40d(P＜0.05).3.The effect on the levels of expression of bax and bcl-2in ovary anduterus of ratsCompared with NC group,the expression of bcl-2decreased while thatof bax increased when administered1.0g.kg-1for60d as well as2.0g.kg-1for40d，50d，60d, repectively(P＜0.05orP＜0.01). The comparison of the groupswhen administered different dosage for the same time: the expression of bcl-2was lower when adminidtered2.0g.kg-1for50d,60d than adminidtered 1.0g.kg-1while the expression of bcl-2showed the opposite result(P＜0.05).The comparison of the groups when administered the same dosage fordifferent time: the expression of bcl-2pro was higher while that of bax waslower when administered1.0g.kg-1for60d than30d (P＜0.05); the expressionof bcl-2decreased while that of bax increased when adminidstered50d,60dthan30d,40d (P＜0.05).Conclusion: The Rhubarb did do a great harm to the ovary and uterus inthe adult femal rats and the toxicity relied on the dosage as well as timeobviously.Part2:the effect of the Rhubarb on the reproductive function in youngfemal ratsObjective: To observe the Rhubarb water infusion, rhubarb decoction10min and30min agent of the effect on the reproductive function in youngfemal rats and the relationship of the dosage.Methods: to separate1004-week femal rats into10groups, includingNC group, test groups (Administrating RWE0.5g.kg-1,1.0g.kg-1and2.0g.kg-1groups, RDA10min0.5g.kg-1,1.0g.kg-1and2.0g.kg-1groups, RDA30min0.5g.kg-1,1.0g.kg-1and2.0g.kg-1groups, respectively) and administered30dand to observe the different indexes including histopathological examination,LH, FSH, E2, bax, bcl-2through HE, Elisa and immunohistochemistryrespectively.Results:1.The effect on the indexes of ovary and uterus in rats1.1The indexes of ovary and uterus decreased when compare the groupof RWE1.0g.kg-1and2.0g.kg-1, RDA10min0.5g.kg-11.0g.kg-1and2.0g.kg-1,RDA30min2.0g.kg-1with NC (P＜0.05orP＜0.01).1.2The comparsion of the group when the rats were administereddifferent dosage by the same methods: The indexes of ovary and uterusdecreased when administered RWE2.0g.kg-1compared with RWE0.5g.kg-1(P＜0.05); So did the groups of RDA10min when the rats were administerd 2.0g.kg-1and1.0g.kg-1compared with0.5g.kg-1(P＜0.05); It showed that thegroup of RDA30min had different significances between the dosages of2.0g.kg-1and0.5g.kg-1(P＜0.05).1.3The comparison of the groups when the rats were administerd thesame dosages through different methods: The indexes of ovary and uterus inrats show signifiacantly different between the groups of RDA10min and RWEas well as RDA30min when administered0.5g.kg-1(P＜0.05); the indexes ofovary and uterus in rats were lower when administered RDA10min1.0g.kg-1compared with RWE1.0g.kg-1and RDA30min1.0g.kg-1(P＜0.05); theindexes of ovary and uterus in rats decreased when the rats were administeredRDA10min2.0g.kg-1compared with RWE2.0g.kg-1and RDA30min2.0g.kg-1(P＜0.05）.2. The effect on the levels of LH、FSH、E2in the serum2.1It showed that the levels of E2and LH、FSH were significantlydifferent in the groups of RWE1.0g.kg-1,2.0g.kg-1, RDA10min，RDA30min2.0g.kg-1compared with NC（P＜0.05orP＜0.01).2.2The comparison of the groups when the rats were adiministered thedifferent dosage through the same methods: The level of E2in the serumdecreased while that of LH and FSH showed a reversed result in the group ofRWE2.0g.kg-1compared the one of RWE0.5g.kg-1(P＜0.05); So did thegroups of RDA10min2.0g.kg-1、1.0g.kg-1compared with the one ofRDA10min0.5g.kg-1(P＜0.05); Also it showed that the same result whencompared the group of RDA30min2.0g.kg-1and RDA30min0.5g.kg-1(P＜0.05）.2.3The comparison of the groups when the rats were administered thesame dosage by different methods: The level of E2in the serum decreasedwhile that of LH and FSH showed a reversed result when compared the groupof RDA10min0.5g.kg-1with the ones of RWE0.5g.kg-1and RDA30min0.5g.kg-1(P＜0.05, so did the comparisons among the groups of RDA10min1.0g.kg-1and RWE1.0g.kg-1as well as RDA30min1.0g.kg-1(P＜0.05, thegroups of RDA10min2.0g.kg-1and RWE2.0g.kg-1and RDA30min 2.0g.kg-1(P＜0.05.3.The effect on the expressions of the bax and bcl-2in the ovary anduterus in the rats.3.1The expressions of bcl-2and bax were significantly different in thegroups of RWE1.0g.kg-1,2.0g.kg-1, RDA10min and RDA30min2.0g.kg-1compared with NC（P＜0.05orP＜0.01).3.2The comparison of the groups when the rats were administered thedifferent dosages through different methods: The expression of bcl-2waslower while that of bax was higher in the group of RWE2.0g.kg-1comparedwith the group of RWE0.5g.kg-1(P＜0.05; So did the comparisons among thegroups of RDA10min1.0g.kg-1,2.0g.kg-1and RDA10min0.5g.kg-1(P＜0.05)as well as the groups of RDA30min2.0g.kg-1and RDA30min0.5g.kg-1(P＜0.05).3.3The comparison of the groups when the rats were administered thesame dosage by different methods: The expression of bcl-2in the ovary anduterus decreased while the expression of bax increased in the group ofRDA10min0.5g.kg-1(P＜0.05);So did the comparisons among the groups ofRDA10min1.0g.kg-1and RWE1.0g.kg-1and RDA30min1.0g.kg-1(P＜0.05)and the groups of RDA10min2.0g.kg-1and RWE2.0g.kg-1and RDA30min2.0g.kg-1(P＜0.05).Conclusion: It showed that Rhubarb did do harm to the ovary and uterusin the young femal rats and the toxicity depended on the dosage. In additionthe toxicity of Rhubarb was negatively correlated with the heating time andthe extract of RDA10min was most toxic.