硫化氢对肝硬化大鼠门静脉压力及肝细胞增殖的影响

摘要

Objective To observe the effect of endogenous hydrogen sulfide (H2S) on cell proliferation and portal vein pressure in cirrhosis rat. Methods A total of 48 female SD rats were randomly divided into 6 groups. Rats in group H, group SH and group PH were made cirrhosis model by injecting carbon tetrachloride ( CCl4). Rats in group S and group SH were injected sodium hydrosulfide NaHS and rats in group P and group PH were injected propargylglycine (PPG) to change the content of H2S in the liver. Rats in group N and group H were injected physiological brine with the same volume. After a intervene of 7 days, laparotomy was performed in all rats to observe the portal vein pressure by method of intubation. The expression of cystathionine γ lyase( CSE)and proliferating cell nuclear antigen( PCNA)in the liver were detected by methods of immunohistochemistry and real time PCR. Results Compared with NF group, the portal vein pressure in HF group increased, the expression of CSE decreased, the expression of PCNA increased (all P <0.01). Compared with HF group, the portal vein pressure in PHF group increased, the expression of CSE decreased, the expression of PCNA increased (all P<0.01). Compared with HF group, the portal vein pressure in SHF group decreased, the expression of CSE increased, the expression of PCNA decreased (all P <0.01). Conclusion The H2S can regulate the portal vein pressure. The possible mechanism may associated with the effect of H2S on the regulation of cell proliferation.%目的 探讨硫化氢(H2S)调节肝硬化大鼠门静脉压力及肝组织细胞增殖的作用及机制.方法 将48只雌性SD大鼠随机分为六组.肝硬化对照组、肝硬化H2S减少组、肝硬化H2S增加组采用四氯化碳复合因素法制作肝硬化模型；正常H2S增加组和肝硬化H2S增加组腹腔注射H2S供体硫氢化钠(NaHS)以增加体内H2S；正常硫化氢减少组和肝硬化H2S增加组腹腔注射H2S代谢酶抑制剂PPG,以减少体内H2S;正常对照组和肝硬化对照组腹腔注射同等剂量的生理盐水.干预7d后门静脉插管法测定各组门静脉压力,取肝脏组织,免疫组化、PCR法观察肝脏组织内细胞胱硫醚γ裂解酶(CSE)及增殖细胞核抗原(PCNA)表达.结果 肝硬化对照组门静脉压力较正常对照组增高,CSE表达降低,PCNA表达增加(P均＜0.01)；肝硬化H2S减少组门静脉压力较肝硬化对照组进一步增高,CSE表达降低,PCNA表达增加(P均＜0.01)；肝硬化H2S增加组门静脉压力较肝硬化对照组降低,CSE表达增高,PCNA表达降低(P均＜0.01).结论 H2S可调节肝硬化大鼠门静脉压力；其机制可能与其调节细胞增殖有关.