Effects Of Small Compound Of Traditional Chinese Medicine On The Histological Structure Of Cerebral Temporal Lobe Cortex, Related Enzyme Activities And Expression On Bax、 C-fos、TGF-β₁Protein Of Ephedrine Addicted Filial Mice

ObjectiveTo get ephedrine addicted filial mice by intraperitoneal inject different doses ofephedrine to pregnant rats in embryonic period. After birth, gavage them smallcompound of traditional Chinese medicine, observing the impaction of smallcompound of traditional Chinese medicine to the development of ephedrine addictedfilial mice whose body weight, cerebral weight, the organizational structure of thetemporal cortex, detecting the impaction of small compound of traditional Chinesemedicine to total antioxidant capacity, hydrogen peroxide activity, reduced glutathionecontent and Bax protein, c-Fos protein and the expression of TGF-β₁of the newbornmice’s temporal cortex. To study the impaction of ephedrine injection duringpregnancy to neonatal mice development, and to explore the protection of smallcompound of Chinese medicine to ephedrine addicted neonatal mice, to analyse thewithdrawal effect of small compound of traditional Chinese medicine.Methods72cases of pregnancy mice were divided into four groups randomly, they wereintraperitoneal injection of different doses （2.0g/L,4.0g/L,6.0g/L） of ephedrinesolution and normal saline after pregnancy for3days, twice a day,0.2ml each timeuntil they delivered15days later; neonatal mice of each group of female rats weredivided equally into two groups after parturition （one group was given smallcompound of traditional Chinese medicine, one group was given normal saline）, thetotal of eight groups （normal control group, normal Chinese medicine group,2.0g/Lexperimental control group,2.0g/L ephedrine group,4.0g/L experimental controlgroup,4.0g/L ephedrine group,6.0g/L experimental control group,6.0g/L ephedrinegroup）, weighing the body weight and cerebral weight when5days,10days,15days.To observe temporal lobe structure of ephedrine addicted filial mice by biologicalmicroscopy, with colorimetric method assay the brain of neonatal mice’s changes ofCAT activity, T-AOC and GSH content, observing Bax protein, c-Fos protein andTGF-β₁expression by immunohistochemical method.Results1) Small compound of traditional Chinese medicine can affect the ephedrine addicted filial mice’s body weight. All of the groups’body weight were lower than thenormal control groups except the normal traditional Chinese medicine group, thedifference was notable or highly significant; the body weight of normal Chinesemedicine groups were higher than normal control group15days after birth, thedifference was significant; different dose of ephedrine groups were significantlyhigher than the same dose of the experimental control group, the difference wasnotable or highly significant;2) Small compound of traditional Chinese medicine can affect the cerebralweight of the ephedrine addicted filial mice cerebral. The cerebral weight of normalChinese medicine groups were higher than the normal control groups, the differenceswere notable （P <0.05）,2.0g/L ephedrine group was lower than the normal controlgroup（P>0.05）, the cerebral weight of the rest groups were lower than control groups,the differences were notable or highly significant; the cerebral weight of2.0g/Lephedrine group was higher than2.0g/L experimental control group （P<0.05）;4.0g/Lephedrine and6.0g/L ephedrine groups were higher than the same dose of theexperimental control group, the difference was highly significant （P<0.01）.3) The Chinese medicine compound can affect the development of ephedrineaddicted filial mice’s cerebral temporal cortex. The thickness of cerebral temporalcortex of normal Chinese medicine group and normal control have no significantdifference, the thickness of the rest groups’ cerebral temporal cortex were lower thanthe normal control group （P<0.05or P<0.01）;4.0g/L and6.0g/L experimentalcontrol groups, the structure of cerebral temporal cortex was unclear, neuronsdysplasia, the thickness of cortical is reduced; the thickness of each dose group offilial mice’s cerebral temporal cortex was significantly higher than the same dose ofthe experimental control group, the difference was significant or highly significant.4) The small compound of Chinese medicine can affect the activity of CAT, andthe content of T-AOC and GSH of ephedrine addicted filial mice’s cerebral. Theactivity of CAT rose highly except. The activity of CAT of2.0g/L experimentalcontrol group and2.0g/L ephedrine group were higher than the normal control group（P<0.05or P<0.01） in the5d and10d, the rest of the group’s CAT activity were lowerthan normal control group （P<0.05or P<0.01）, each dose ephedrine group’s CAT activity was significantly higher than the same dose of the experimental control group,the difference was notable or highly significant. Within15days after filial mice’sbirth, the T-AOC level of each group has different increased, the T-AOC level ofChinese medicine group was higher than the normal control group, the difference wassignificant;2.0g/L experimental control group and2.0g/L ephedrine group werehigher than the normal control group at the5th day （P <0.05）, the T-AOC level of therest groups in various periods were lower than the normal control group, thedifference was notable or highly significant. The T-AOC level of each dose ofephedrine group was higher than experimental control group of the same dose（P<0.05or P<0.01）.In the filial mice’s development process within15days after birth, the content ofGSH of ephedrine addicted filial mice’s cerebral were increased, the content of GSHof Chinese medicine group in each period was lower than the normal control group,no significant difference; the content of GSH of2.0g/L experimental control groupand2.0g/L ephedrine gradually restored to normal levels, the GSH levels of the restgroups were lower than normal control group, the difference was notable or highlysignificant.In each dose group of ephedrine experimental control group higher thanthe same dose（P<0.05or P<0.01）.. In the filial mice’s development process within15days after birth, the activity of CAT, the content of T-AOC and GSH graduallyrestored to normal levels, express a dose-response relationship, the lighter damage tothe embryo the stronger recuperability, after intragastric administration of compoundof traditional Chinese medicine, the resilience of the cerebral tissue speed up, theeffect is significant and faster compared with the same dose of the experimentalcontrol group.5) The small compound of Chinese medicine can affect expression of Baxprotein, c-Fos protein and TGF-β₁of ephedrine addicted filial mice’s cerebraltemporal lobe cortex. Inject ephedrine in early pregnancy, the number of cells whichexpress Bax protein, c-Fos protein and TGF-β₁were higher than the normal controlgroup （P<0.05or P<0.01）; in the filial mice’s development process within15daysafter birth, the expression of Bax protein, c-Fos protein and the of TGF-β₁havedecreased. The three indicators decreased more significantly in doses of ephedrine group than the same dose of the experimental control group, the difference wasnotable or highly significant （P<0.05or P<0.01）.Conclusion1) After injecting ephedrine in pregnant mice, the development of filial mice’sbrain was affected for long term. Exposure to ephedrine at early trimester ofpregnancy stage had toxic effects on the neurons migration in the filial mice’s brain.Cerebral weight of filial mice, thickness of each cerebral temporal lobe cortex andnumber of neurons were still lower than that of the control group at postnatal15days,which might be the extending results of direct toxicity of ephedrine and itsmetabolites on embryonic neurons. Cerebral weight of filial mice, thickness of eachcerebral temporal lobe cortex and number of neurons were still higher than that of thecontrol group at postnatal15days, which might be the traditional Chinese medicineadjusting results of differentiation and migration of nerve cell.The traditional Chinesemedicine stimulate production and differentiation of nerve cell, strengthen protheticcapability of neuroglial cells to impaired nerve cell,lead to high of cerebral weight offilial mice, thickness of each cerebral temporal lobe cortex and number of neurons.2) After injecting ephedrine in pregnant mice, ephedrine can enter embryothrough placental membrane, addiction of filial mice at embryonic stage. Ephedrineand its metabolic product can enter filial mice through milk, and restraint appetite,decreased body weight. The traditional Chinese medicine can increase metabolism ofpregnant mice,adjust immune system of pregnant mice, clear free radical, enhancedigestion and absorptive function, promote appetite，which make body weight gain.3) Ephedrine cause degrade of CAT、T-AOC activity and GSH content. Freeradical can not remove quickly,lead to change of histological structure in thecerebrum.But the traditional Chinese medicine can clear free radical and make theantioxygen capability high. Compared with ephedrine group CAT、T-AOC activityand GSH conten of the traditional Chinese medicine in cerebrum increased and abilityof clear free radical reinforced.4) Ephedrine affected histological structure in the cerebrum of the developingfilial mice and breakdown the free radical of filial mice. The positive expression ofBax protein、c-fos protein and TGF-β₁in the cerebrum of filial mice obviously increased with injection ephedrine than that of the control at the each developmentalperiod. The cerebrum of filial mice at the different developmental stages weredamaged by ephedrine, with the increase of the dosages of ephedrine and theextension of time, which showed an evident dose-effect relationship. Afteradministration of the traditional Chinese medicine at15day,compared with thecontrol group，the positive expression of Bax protein、c-Fos protein and TGF-β₁decreased gradually in the cerebrum of filial mice. It indicated that the traditionalChinese medicine inhibited apoptotic of brain cell.