膳食碘过量对大鼠脑中胆囊收缩素基因表达的影响

目的 观察过量碘膳食对成年大鼠脑中胆囊收缩素(CCK)基因表达的影响,探讨发生机制.方法 选用断乳1月龄的Wistar大鼠,按体重随机分为5组,每组30只,摄碘量分别为6.15(A组)、30.75(B组)、61.5(C组)、307.5(D组)、615 μg/d(E组),各组均饲以正常鼠料,饮用含不同碘浓度的水,饲养3、6个月后处死,用放射免疫分析方法测定血清甲状腺激素水平;取脑组织,采用RT-PCR方法检测脑组织CCK mRNA的表达.结果 3个月时,E组大鼠血清总甲状腺素T4(TT4)(45.2±13.7)nmol/L、总甲状腺素T3(TT3)(0.65±0.20)nmol/L、游离甲状腺素T3(FT3)(0.93±0.45)pmol/L、游离甲状腺素T4(FT4)(7.07±2.43)pmol/L、反三碘甲状腺原氨酸(rT3)(0.15±0.04)nmol/L均明显低于A组的TT4(76.0±18.8)nmol/L、TT3(1.34±0.41)nmol/L、FT3(2.45±0.62)pmol/L、FT4(15.12±3.40)pmol/L、rT3(0.24±0.04)nmol/L(F值分别为14.68、16.03、21.16、20.25、13.52,P＜0.01);C组、D组的FT3水平与A、B组比较降低(F=21.16,P＜0.05);D组的rT3水平与A、B、C组比较也有降低(F=13.52,P＜0.05).6个月时,E组TT4(51.84±15.83)nmol/L、TT3(0.77±0.22)nmol/L、FT3(0.74±0.28)pmol/L、FT4(6.88±2.23)pmol/L、rT3(0.14±0.03)nmol/L均低于其余各组(F值分别为6.05、12.22、11.25、13.42、5.89,P＜0.05).E组大鼠脑中CCK mRNA水平在3个月和6个月时与其余各组比较均降低(F值分别为4.04、3.95,P＜0.01).相关分析结果显示:3、6个月时血清FT4水平与CCK mRNA水平间存在着线性相关趋势(r值分别为0.990、0.948,P＜0.05).3个月、6个月时血清FT3水平与CCK mRNA水平间不存在线性相关关系(r值分别为0.970、0.932).结论 高于正常100倍的碘摄入会引起大鼠脑中CCK mRNA水平的降低;在此过程中,FT4水平的改变较FT3而言可能起着更重要的作用.

Overdose of iodine on expression of CCK gene in rat brains

OBJECTIVE: To observe the effect of overdose iodine on the expression of CCK gene in brains of rats and identify the possible mechanisms. METHODS: One-month weaning Wistar rats were randomly divided into five groups which were fed with normal feedstuff and water supplemented with different concentrations of potassium iodide, named A group (iodine ration was about 6.15 microg per day), B group (iodine ration was about 30.75 microg per day), C group (iodine ration was about 61.5 microg per day), D group (iodine ration was about 307.5 microg per day) and E group (iodine ration was about 615 microg per day). Rats were sacrificed after being fed for three or six months. Then serum thyroid hormones were measured by radioimmunoassay and the mRNA level of CCK gene was studied by using RT-PCR technique. RESULTS: At the end of three months, the values of thyroid hormones in E group TT4 (45.2 +/- 13.7) nmol/L, TI'3 (0.65 +/- 0.20) nmol/L, FT3 (0.93 +/- 0.45) pmol/L, FT4 (7.07 +/- 2.43) pmol/L, rT3 (0.15 +/- 0.04) nmol/L] were all lower than those in A group TT4 (76.0 +/- 18.8) nmol/L, TT3 (1.34 +/- 0.41) nmol/L, FT3 (2.45 +/- 0.62) pmol/L, FT4 (15.12 +/- 3.40) pmol/L, rT3 (0.24 +/- 0.04) nmol/L]. There were significant differences between E group and A group on the levels of serum TH (F values are 14.68, 16.03, 21.16, 20.25, 13.52 respectively, P < 0.01); FT3 levels in C and D groups were significantly decreased as compared to A and B groups (F = 21.16, P < 0.05). rT3 level in D group was significantly decreased compared with A,B and C groups (F = 13.52, P < 0.05). At the end of six months, the levels of serum TH in E group (TT4 (51.84 +/- 15.83) nmol/L, TT3 (0.77 +/- 0.22) nmol/L, FT4 (6.88 +/- 2.23) pmol/L, FT3 (0.74 +/- 0.28) pmol/L, rT3 (0.14 +/- 0.03) nmol/L) were lower than those in any other groups (F values were 6.05, 12.22, 11.25, 13.42, 5.89 respectively, P < 0.05). At the end of both three and six months, the mRNA levels of CCK gene in E group were lower than any other groups (F values were 4.04, 3.95 respectively, P < 0.01). The results of correlation analysis showed that serum FT4 had linear correlation with levels of CCK mRNA (r values were 0.990, 0.948 respectively; P < 0.05); However serum FT3 had no linear correlation with the levels of CCK mRNA (r values are 0.970, 0.932 respectively). CONCLUSIONS: Exposure to overdose of iodine (iodine ration was 100-fold higher than that of A group) could decrease the mRNA level of CCK gene. Compared with FT3, FT4 might have more important role on the regulation of CCK mRNA induced by excess of iodine.