CAJ | 학술논문

目的：观察山奈酚（ Kaempferol，KA）对肝组织转化生长因子（TGF）-β1/Smads信号通路的影响，探讨其预防血吸虫病肝纤维化的作用机制。方法40只BALB/c小鼠随机分为正常对照组（8只）、吡喹酮组（8只）、吡喹酮+山奈酚4个剂量组（5、10、15、20 mg/kg）（每组6只）。除正常对照组外，其余5组小鼠同时感染日本血吸虫，感染6周后吡喹酮组及吡喹酮+山奈酚4个剂量组给予吡喹酮连续灌胃2 d，其后吡喹酮+山奈酚4个剂量组分别以5、10、15、20 mg/kg山奈酚连续灌胃6周，吡喹酮组予以等量生理盐水灌胃6周。干预结束后处死小鼠并取肝脏，以苏木精-伊红（HE）和Masson胶原纤维染色法观察小鼠肝虫卵肉芽肿面积和肝纤维化程度；以免疫组化染色观察小鼠肝组织TGF-β1、Smad2/3、Smad7蛋白的表达情况；采用实时荧光定量PCR检测肝组织Smad2/3、Smad7 mRNA的表达情况。结果与吡喹酮组小鼠相比，吡喹酮+山奈酚4个剂量组肝脏虫卵肉芽肿面积较小，纤维化程度较轻，肝组织Smad2/3蛋白及其mRNA表达水平较低，Smad7蛋白及其mRNA表达增加，差异均有统计学意义（P均<0.05）。结论山奈酚通过减少肝组织内TGF-β1、Smad2/3的表达及增加Smad7的表达，能明显减轻吡喹酮杀虫治疗后虫卵肉芽肿所致肝纤维化。
목적：관찰산내분（ Kaempferol，KA）대간조직전화생장인자（TGF）-β1/Smads신호통로적영향，탐토기예방혈흡충병간섬유화적작용궤제。방법40지BALB/c소서수궤분위정상대조조（8지）、필규동조（8지）、필규동+산내분4개제량조（5、10、15、20 mg/kg）（매조6지）。제정상대조조외，기여5조소서동시감염일본혈흡충，감염6주후필규동조급필규동+산내분4개제량조급여필규동련속관위2 d，기후필규동+산내분4개제량조분별이5、10、15、20 mg/kg산내분련속관위6주，필규동조여이등량생리염수관위6주。간예결속후처사소서병취간장，이소목정-이홍（HE）화Masson효원섬유염색법관찰소서간충란육아종면적화간섬유화정도；이면역조화염색관찰소서간조직TGF-β1、Smad2/3、Smad7단백적표체정황；채용실시형광정량PCR검측간조직Smad2/3、Smad7 mRNA적표체정황。결과여필규동조소서상비，필규동+산내분4개제량조간장충란육아종면적교소，섬유화정도교경，간조직Smad2/3단백급기mRNA표체수평교저，Smad7단백급기mRNA표체증가，차이균유통계학의의（P균<0.05）。결론산내분통과감소간조직내TGF-β1、Smad2/3적표체급증가Smad7적표체，능명현감경필규동살충치료후충란육아종소치간섬유화。
Objective To investigate the influence of kaempferol on transforming growth factor(TGF)-β1/Smads signal trans-duction in liver tissue of mice with schistosomiasis liver fibrosis. Methods Forty BALB/c mice were randomly divided into a normal control group(8 mice),a praziquantel group(8 mice ),and 4 praziquantel+kaempferol groups with different kaempfer-ol dosages(5,10,15,20 mg/kg respectively,6 mice each group). Besides the normal control group,all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks,the praziquantel group and the 4 praziquantel+ kaempferol groups were treated with praziquantel 500 mg/(kg · d) for 2 d,then the mice in the praziquantel group were drenched with normal saline for 6 weeks,and those in the 4 praziquantel+kaempferol groups were drenched with kaempferol 5, 10,15,20 mg/kg respectively for 6 weeks. After the treatment,all the animals were sacrificed by the cervical dislocation meth-od,and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1,Smad2/3,Smad7 proteins were measured by the immunohistochemical method,and the mRNA lev-els of the 3 proteins were detected by RT-PCR. Results Compared with the mice in the praziquantel group,the areas of egg granuloma of the liver of the mice in the 4 praziquantel+kaempferol groups were smaller,and the degrees of the hepatic fibrosis of the mice were lesser,and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P<0.05),while the expression of Smad7 at protein and its mRNA level were significantly higher(all P<0.05). Conclu-sion By decreasing the expressions of TGF-β1 and Smad2/3,and increasing the expression of Smad7,kaempferol can signifi-cantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.