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目的观察妊娠肝内胆汁淤积症(ICP)孕鼠肝脏、胎鼠脑组织结构变化;分析神经肽Y(NPY)在妊娠期肝内胆汁淤积症(ICP)胎鼠脑组织中的表达及意义。方法选择孕15 d SD大鼠,用孕酮及乙炔雌二醇建立孕鼠ICP模型,观察孕鼠肝脏和胎鼠脑组织的病理变化;应用免疫组织化学染色方法及图像分析检测ICP孕鼠(20例,实验组)及正常孕鼠(20例,对照组)脑组织中NPY的表达及定量。结果 ICP孕鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆酸(TBA)明显升高;光镜下见部分肝细胞有颗粒样变性和空泡变性。电镜下见肝组织中毛细胆管扩张、微绒毛肿胀,毛细胆管周围肝细胞内见电子致密物沉积。胎鼠脑组织疏松,空泡样变性明显,部分细胞溶解,甚至消失。实验组胎鼠脑组织NPY表达免疫阳性神经元主要位于海马区,免疫阳性细胞被染成棕黄色,免疫阳性颗粒主要分布在胞质和细胞膜表面。对照组海马区仅少部分细胞膜着色或无免疫着色。胎脑组织NPY的免疫组化结果用图像分析仪测定,结果显示:实验组NPY平均光密度值(1.0486±0.0182)明显高于对照组的(0.6297±0.0278),两者比较有显著性差异(P<0.05)。结论 ICP母鼠肝脏及胎鼠脑组织有明显病变,胎鼠脑组织中的NPY表达升高,可能与胎脑组织受损有关。
Objective To observe the changes of brain tissue in liver and fetal rat during intrahepatic cholestasis of pregnancy (ICP), and to analyze the expression and significance of neuropeptide Y (NPY) in brain tissue of intrahepatic cholestasis of pregnancy (ICP). Methods 15-day-old pregnant SD rats were selected. ICP model was established with progesterone and ethinyl estradiol to observe the pathological changes in the liver and fetal rat brain. Immunohistochemical staining and image analysis were used to detect ICP pregnant rats 20 cases, experimental group) and normal pregnant rats (20 cases, control group). Results The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) in ICP pregnant rats were significantly increased. Part of hepatocytes were degenerated by light microscope and vacuolar degeneration under light microscope. Electron microscope, see the bile duct dilatation of the liver tissue, microvilli swelling, see within the hepatocytes in the bile duct around the deposition of electron dense material. Fetal brain tissue loose, vacuolar degeneration obvious, some cells dissolved, or even disappear. The NPY positive neurons in the experimental group were mainly located in the hippocampus. The immunopositive cells were stained brown and the immunopositive granules were mainly distributed on the cytoplasm and the cell membrane. Control group, only a small part of the hippocampal cell membrane coloring or no immunopotentiation. The results of immunohistochemistry of NPY in fetal brain tissue were analyzed by image analyzer. The results showed that the average optical density of NPY (1.0486 ± 0.0182) in the experimental group was significantly higher than that of the control group (0.6297 ± 0.0278), the difference was significant P <0.05). Conclusion The ICP rat liver and fetal rat brain tissue obvious lesions, fetal rat brain NPY expression may be related to fetal brain tissue damage.