头孢曲松钠对豚鼠胆囊收缩功能影响的实验研究

Experimental study of ceftriaxone sodium on the effect of gallbladder contraction function in guinea pigs

目的研究头孢曲松钠对豚鼠胆囊收缩功能的影响,以更好地指导临床用药。方法将60只豚鼠随机分为四组,A组(空腹对照组)、B组(饱餐对照组)、C组(空腹实验组)和D组(饱餐实验组)。对实验组C组、D组肌肉注射头孢曲松钠,建立头孢曲松钠相关性胆囊模型。造模成功后,对四组豚鼠的胆囊体积、胆汁量、胆汁及血清中胆汁酸、丙氨酸氨基转移酶(ALT)及胆囊收缩素(CCK)含量及胆囊组织中胆囊收缩素A受体(CCK-AR)基因的表达等进行测定。结果 C组和饱餐实验组的胆囊体积均显著高于A组和B组,表明头孢曲松钠可显著增高豚鼠的胆囊体积(P<0.05);实验组豚鼠的胆汁量均显著高于对照组(P<0.05),表明实验组豚鼠胆囊内出现胆汁淤积。胆汁中实验组豚鼠的胆汁酸水平均显著低于对照组;而血清中实验组豚鼠的胆汁酸水平均显著高于对照组(P<0.05),表明实验组胆汁中胆汁酸的浓度出现下降,而血清中胆汁酸的含量则呈上升趋势。实验组豚鼠的ALT含量显著高于对照组豚鼠,表明头孢曲松钠可致豚鼠ALT水平升高。血清及胆囊组织中实验组的CCK水平均显著低于对照组;实验组胆囊组织中CCK-AR mRNA的相对表达量均显著低于对照组(P<0.05)。结论头孢曲松钠可降低血清及胆囊组织中CCK的含量,并抑制CCK受体基因的表达,从而减弱胆囊的收缩功能,导致胆囊内出现胆汁淤积,促进结石的形成。为减少此类不良反应的发生,临床上应尽量避免长期、大剂量的使用头孢曲松钠。

Objective To study ceftriaxone sodium on the effect of gallbladder contraction function in guinea pigs,in order to guide clinical therapy better. Methods 60 guinea pigs were randomly divided into four groups,A（ fasting group）,B（ full control group）,C（ fasting experiment group） and D（ full experimental group）. The experimental group C,D were given intramuscular injection of ceftriaxone sodium,the establishment of ceftriaxone sodium correlation between gallbladder model. After the success of modeling,gallbladder volume,the amount of bile,bile and serum bile acid content,ALT content and CCK content and the expression in gallbladder tissue of four groups were determined. Results Gallbladder volume of fasting experimental group and full meal experimental group were significantly higher than that of fasting control group and the full meal control group（ P 〈0. 05）. It showed that ceftriaxone sodium could significantly increased the volume of gallbladder of guinea pigs（ P 〈0. 05）. It showed that the experimental group appeared in the guinea pig gallbladder cholestasis. Bile acid level in guinea pigs in the experimental group was significantly lower than that of the control group; bile acid levels in the serum of experimental group were significantly higher than that of control group（ P 〈0. 05）. It showed that bile and bile acid concentrations of the experimental group declined,but the content of bile acid in serum increased. The content of ALT in guinea pigs of experimental group was significantly higher than that of control group. This indicated that ceftriaxone sodium could result in ALT levels of guinea pigs increased. CCK levels of serum and gallbladder tissue were significantly lower than those of control group. Relative expression of CCK- AR mRNA of gallbladder tissue in the experimental group were significantly lower than those of the control group（ P 〈0. 05）.Conclusion Ceftriaxone sodium can decrease CCK content of serum and gallbladder tissue and inhibit the expression of CCK receptor gene,thus weaken the contraction function of gallbladder,leading to the gallbladder cholestasis,it can promote the formation of stones. In order to reduce occurrence of such adverse reaction we should try to avoid long- term,high dose of ceftriaxone sodium in clinic.