1 %,0 T C' D ] D QA ; 1. 3 `< ;! I H `< [5] : A ` ^ ^ 7 ; Z 2mL,VPA 200mg kg - 1,LTG 20mg kg - 1,P2 b" 1 2 3d P 1,X 4 \,b"$ 4 2 3d #,, 30d 1. 4 %ATQ7]

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1 1 8 Journal of Ningxia Medical University : (2013) [_ D Q Q ; 1,. 2, 3, < 4 (1., ; 2., ; 3.!. \, ; 4. ", ) U :6 T (Valproate sodium,vpa)7c'(lamotrigine,ltg) D D QA V# 28 Z 8 B SD D? 4 :9 ; T (VPA )7C ' (LTG ) ; VPA LTG : (KA)!, ; I b" Z T C' 1 I,2 3d # 1, b" 30d,P %4 >c ], T :Q] 9 (Luteotropic hormone,lh) $ K (Follie stimulating hormone,fsh) % (Testosterone,T) L (Progesterone,P) (Estradiol,E2), $c $&,$&#, HE, \ Image - pro Plus 6. 0 H a WX ; :,] % 9 Q' (P < 0. 05),L Q (P > 0. 05); ; 7 VPA 9 %;VPA, ^_, (P < 0. 01);VPA :,] 9 7 % ' (P < 0. 05),$ K 7L (P < 0. 05);LTG Q A W- ( (P > 0. 05);VPA : LTG Q,A W- ((P < 0. 05) WA D ; D Q, T C' D D,-.: T ;C'; /01:R711. 5! ;;D ; % :A N,34 S $& K (PCOS) `L!D I D ] 0 [1] \ % $&S F [2] T (Valproate sodium,vpa)v M A (, D %M VPA I `L ] 0 X PCOS A I [3,8],AEDs D (AEDs)7 X I D I A( 56 ;,O VPA 7C'(LTG)`< ] D QA, < 7 A` MU \ 1 Y GV# 1. 1 \ : \ Spague - Dawley(SD)8 B D 2: : %56 '(2011CB512115), 160 ~ 789:: (1975 -),, 3, U&256,56 : 8 E - mail:shiqing1107@163. com ; 78: /,3 E - mail:zhanglingwu@ hotmail. com 220g,b\ #U T 01 A 4,, K 21 ~ 25, ( 50%~ 60% 2 9 %A 28 Z? 4,, Y &, KA!,@ ; VPA LTG,2 7 Z 1. 2 ; 5g L - 1 T#) (1mL 100g - 1 )* <,UQP! Q,01, Paxinos and Watson +,, :L* & CA3 (- Q P. 5. 0mm, / B 5. 0mm,0 C 5 0mm), - ;1 B, HF=0,>c: 1. 0μL(0. 4μg μl - 1 )LM,P 10 ~ E 5min NN -BC, KO, 2 K Racine [4], 6 :0 :9 ;Ⅰ: & 3 4, 56;Ⅱ: 7& 34, 8 O ;Ⅲ: Ⅱ^_,( 9 4;Ⅳ: Ⅲ^_, 9: ;Ⅴ:Ⅳ^_ N ; N 3 Ⅳ ~ Ⅴ I

2 1 %,0 T C' D ] D QA ; 1. 3 `< ;! I H `< [5] : A ` ^ ^ 7 ; Z 2mL,VPA 200mg kg - 1,LTG 20mg kg - 1,P2 b" 1 2 3d P 1,X 4 \,b"$ 4 2 3d #,, 30d 1. 4 %ATQ7] Q %ATQ A( % 4 ~ 5d, L G A O %A [6] 2 8:00 L G \, # %: 8$ 17 ~ 21h,Q%$ L G &V " G, A G %: 8$ 9 ~ 15h,$ $, \ &V "A G G %: $ 10 ~ 14h, 9, \ G A G " G %: 8 $ 60 ~ 70h,Q%9, \ G G ^ \ A G, %X A A G N $ ( A G N $ %$ % % P 5d,# D % D % %P 5d # % ( D % D %) A=3 CZ7 4 `< 30d #, : `<,-^, P % D %P 5d $, 5 g L - 1 T # ) (1mL 100g - 1 )* <,b#` JK>c ] 5mL, 10mL 1X, R,4 3000r min - 1 "# 3min c], X, ( :Q $Qc $ &,# 40g L - 1 S RSUQ, Z-\, HE, \ Image - pro Plus 6. 0 H a 1. 5 W- M SPSS \ H W - - T ± A /,L4 $9a A $, TA = A (One way ANOVA), LSD ;P A W- ( 2 WX 2. 1 ;! Q : :L CΑ3, ', I? \ ; GN 6, N V< 7O7A> 9>=, H - 4D, : >? ' IX,VZ@A>? ; ; 19 \ (VPA [ 1 Z,LTG b" $N] [ 1 Z) 2. 2 %A ; `< 15d,4 Z N %,L \ A VPA `< 13d,6 Z N %,3 Z % 8 ~ 9d,2 Z A,1 Z G % LTG 2 Z % 7d, A , $& A \ % VPA A, ^,A W- ((P < 0. 01) LTG, A W- ((P > 0. 05);4 $& A W- ((P > 0. 05), B $ 30d Z ( 珋 x ± s) n, / g $& / mg LTG ± ± VPA ± ± NS ± ± ± ± : VPA P < 0. 01;: NS P < 0 01;: P < 0. 05, P < ] D Q VPA FSH Q LTG (P < P < 0. 01);LTG ; FSH Q A W- ((P > 0. 05) VPA ; LH Q ' (P < 0. 01,P < 0. 05), VPA LH Q P ; (P < 0. 05), P LTG (P < 0. 01);LTG LH Q A W - ((P > 0. 05) E2 Q A W- ((P > 0. 05) VPA ; P Q (P < 0. 01);VPA P Q LTG ^ (P < 0. 05);LTG P Q A W- ((P > 0. 05) VPA T Q LTG ; ' (P < 0 05);LTG T Q A W- ((P > 0. 05), 2

3 Q ( 珋 x ± s) n FSH /(miu ml - 1 ) LH /(miu ml - 1 ) E2 /(pg ml - 1 ) P(ng ml - 1 ) T /(ng dl - 1 ) LTG ± ± ± ± ± VPA ± ± ± ± ± ; ± ± ± ± ± ± ± ± ± ± F P A : P < 0. 05, P < 0. 01;: LTG P < 0. 05, P < 0. 01;: NS P < DD 34 b$& A L 7 A! 0 :$& I I, B A W(! $&,HPOA)! D 0 (GnRH) 0 D A $&I,$& AD! - 0 C, HPOA A N! A A K $7 %A F `! - 0,)! GnRH A I, V>? A,!E W!AI,E W A9,& HPOA I \ \>? 9 % Q 7] [2 - VPA V( +, N - R ^ - D - (NMDA) A.,- D γ - ^ (GABA)0, Y A 56^/, DH VPA $,PCOS A? AED [8] A `@ LTG V( ;A, ^ K,34 PH D, P450 MOR RELL [9] 0, D 4 VPA, Q, 3. 5%, 4 LTG 1 Q,I % 8, Q Roste 0 [10] 56 \, % LTG A $& a, VPA O ZD % F D A, V A^ 9:,D % 56,VPA ` 35 < 13d 6 Z N %, ; 15d 4 Z %,LTG 2 Z % 7d A 9 U/, a VPA %A ^ 56,\ % ; :, ^(P < 0. 05),<: Scharfman [11] A 56(@ \,H-N b I A! :( V. D - -!, ( V D - *! A ^ P<, H H- $,E W7 V -N 3 A, ` P J,,GAQG 3 4A bp -! A, $7 %A F H W,!I,-I,- H-,S,$, 56, VPA `< A, 3 ^,: A W- ((P < 0. 01), VPA V( + J, KLJK] V, J A β 2,$ J,& Martin [12],VPA,,-! GABA WAND, -I, 7 M bq :, VPA I 7 56 $,LTG A,: A` ^(P > 0. 05) bq :,LTG ` 7 I ] D Q56JU^/:1 ; :,] T LH Q', P Q \,$&A 34b$ 7$& K bq :, V F! - 0,) GnRH D?,, QA LH K, $ G A

4 1 %,0 T C' D ] D QA 2 1 T K,S,LH!, N%N, FSH,) LH / FSH 56 \,FSH V$ M A, HO $ O $ A M, \ N G ), H E2 A K : bq :, QA FSH K,Z )$& $ M (Q,` O $ 7 O $ $ $, $ & S D [13] bpj $ X ) AI `,` 2,< V SA 56,$ %$ ` L, V LH $ NA,L 34 b $ $ A9 G $ A9,\ P Q, 3 4V: $ 9 I0 2VPA `< ] T LH Q' 3 ^_,FSH P Q ^ bp VPA V( P450,, Q M% A )] N D A % Q ' Nelson - DeGrave 0 [14],VPA P$ G, AK 7,S \,!V HPOA A #,GnRH A 0 D $&D GnRH K A C <= C 7 W A (, S GnRH A GABA V 4A(,! 0 Q 0? A, $&I, GABA ^ X S D A DJK [15] b Q : VPA γ - ^ GABA, P H - P - O,K GnRH,) LH,,H U % Q L S A J 2 ( (E1), E1 / E2 A ' %,!70 A $, H LH A ] V P COS 34A $,^_, A% C FSH A LH / FSH ',< K PCOS A 56,VPA \ ` W b Q a,vpa,-o U A, )] D JKV (SHBG) Q,bQ P QA $& %9 % P GnRH NA? 7,,LH,S, K O$&7 K 7 3 \ ^/,LTG ] D Q A W- ( (P > 0. 05), LTG A] LH T Q VPA A^_(P < 0. 01) bq,ltg ` H GnRH - LH, LH / FSH A,, ],` ^,, T LH FSH QA^_ D S $ & 7 PCOS V 3 H( A5 6 VPA : PCOS A0, D ) VPA $,MP:I %A T D QA, 4$P:$&J QA,3RK LTG ^_ : [1] Sojrvi JI,Taubll E,Herzog AG. Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy [J]. CNS Drugs,2005,19 (3 ): [2] ST. ; % $& aa [J]. % R : >,2011,32(2): [3] UVW, X. Y Y ] D Q A [J]. 5 6,2007,24 (10):1752. [4] Rcine R,Okujava V,Chipashvili S. Modification of sei zure activity by electrical stimulation[j]. Electroen cephalogr Clin Neurophysiol,1972,32: [5] -R. ) T ( ( ] 7 Q A [J]. " L, 2007,9(3): [6] Freeman ME. The neuroen docrine control of th e o varian cycle of the rat [M]/ / Knobil E,Neil l JD (Eds). The Physiology of Reproduct ion. Raven Press Ltd. New York:Raven Press,1994: [7] Hum KM,Megna S,Burnham WM. The effects of right and left amygdale a kindling on the female reproductive systemin rats [J]. Epilepsia,2009,50(4): [8] Pfeifer SM,Kives S. Polycystic vary syndrome in the adolescent[j]. Obst Gynecol Clin North Am,2009,36 (1): [9] Morrell MJ,Hayes FJ,Sluss PM,et al. Hyperandro genism,ovulatory dysfunction,and polycys - tic ovary syndrome with valproate versus lamotrigine [J]. Ann Neuro,2008,64(2):

5 [10] Roste LS,Tauboll E,Berner A,et al. Valproate,but not lamotrigine,induces ovarian morphological chan ges in Wistar rats[j]. Exp Toxicol Pathol,2007, 52: [11] Scharfman HE,Kin M,Hintz TM,et al. S eizures and reproductive function:insights from female rats with epilepsy[j]. Ann Neurol,2008:64(6): [12] Martin CK,Han H,Anton SD,et al. Effect of valproic acid on body weight,food intake,physical activity and hormones:results of a randomized controlled trial [J]. Psychopharmacol,2008,113(12): [13] _,S $& K [M]. 7 >.. P :. N>$,2008: [14] 6,6,Z,0. VPA $ G I0[ K A[J]. : L,2005,21(11): [15] Hurley JH,Ballard CJ,Edenberg HJ. Altering the rel ative abundance of GABA A receptor subunits chan ges GABA - and ethanolresponses in Xenopus oocytes [J ]. Alcohol Clin Exp Res,2009,33 (6 ): ( : ()) Effects of Valproate and Lamotrigine Acid on Serum Sex Hormone Levels in Female Rats with Epilepsy SHI Qing, ZHANG Ling - wu, SUN Tao, BAI Yun - xian (Ningxia Med. Univ.,Yinchuan ) Abstract:Objective To detect the serum concentrations of folliele stimulating hormone(fsh),luteotropic hormone (LH),estradiol(E 2 ),Progesterone(P)and Testosterone(T)of epileptic female rats induced by Kainic acid(ka)and to explore the effects of valproate and lamotrigine acid on serum sex hormone levels in female rats with epilepsy. Methods 8 - week - old Sprague - Daweley 28 rats were divided randomly into four groups. Controls were fed normal saline 2mL every day and rest groups were established epileptic modle induced by Kainic acid(ka),randomly administered with VPA,LTG and NS by intragastric administration for 30 days. Weight was monitored per 3 days and dose was adjusted according to body weight. Estrous cycles were monitored with daily vaginal smears. After 30 days,bleeding,separating of ovary organs in their diestrus. Serum FSH,LH,E2,P and T level were determined using the electrochemical luminescence method. Results VPA group showed significant weight gain (P < 0. 01). The level of LH was significantly increased in the VPA and NS groups compared with control group. The level of FSH was significantly decreased in the VPA group com pared with the control and LTG groups. the level of T was significantly increased in the VPA group compared with LTG and control groups. The level of P was significantly decreased in the VPA group compared with con trol,ltg and NS groups. Conclusion Valproic acid sodium is easier to cause sex hormone secretion disorder than lamotrigine. Key words:valproate sodium;lamotrigine;epileptic modle;estrus cycle;sex hormone N #$ N A "# 2 rpm /,<V Q A\ 9 A\ V:L "#$ r min - 1 /;L "#$ I "# g /,g VD, V ( ] &)

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