目的探讨乌梅提取物对纳米细菌(NB)导致的大鼠肾草酸钙结石形成的影响及其机制。方法 30只大鼠随机分为A、B、C、D、E组各6只。A组第1天以生理盐水1 m L尾静脉一次性注射作为正常对照,B、C、D、E组均于第1天以尾静脉一次性注射NB混悬液1...目的探讨乌梅提取物对纳米细菌(NB)导致的大鼠肾草酸钙结石形成的影响及其机制。方法 30只大鼠随机分为A、B、C、D、E组各6只。A组第1天以生理盐水1 m L尾静脉一次性注射作为正常对照,B、C、D、E组均于第1天以尾静脉一次性注射NB混悬液1 m L建立大鼠草酸钙结石模型。A、B组第2天起均以生理盐水2m L/d灌胃,C、D、E组第2天起分别以0.05、0.10、0.15 g/m L乌梅提取物2 m L/d灌胃。各组干预4周后,收集24 h尿液,应用高锰酸钾褪色法测定尿液草酸(Ox)水平,全自动生化仪测定尿液Ca^(2+)水平,柠檬酸试剂盒测定尿液柠檬酸水平,8-羟基脱氧鸟苷(8-OHDG)测试盒测定尿液8-OHDG水平。取左侧肾脏,行HE染色观察肾组织草酸钙结晶形态,行结晶量分级评分。采用硫代巴比妥酸法检测肾组织丙二醛(MDA)水平。结果 B组尿液Ox、Ca^(2+)、8-OHDG水平均高于A组,柠檬酸水平低于A组(P均<0.05);C、D、E组尿液Ox、Ca^(2+)、8-OHDG水平均低于B组,柠檬酸水平均高于B组(P均<0.05)。A组无草酸钙结晶,B组草酸钙结晶明显较多,C、D、E组草酸钙结晶数量较B组明显减少。B组草酸钙结晶量评分高于A组,C、D、E组草酸钙结晶量评分均低于B组(P均<0.05)。B组肾组织MDA水平高于A组,D、E组肾组织MDA水平均低于B组(P均<0.05)。结论乌梅提取物对NB所致的大鼠肾草酸钙结石具有明显的抑制作用,其机制可能与降低大鼠尿液Ox水平,进而减少尿Ca^(2+)排泄、减轻脂质过氧化损伤有关。展开更多
AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesi...AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.展开更多
文摘目的探讨乌梅提取物对纳米细菌(NB)导致的大鼠肾草酸钙结石形成的影响及其机制。方法 30只大鼠随机分为A、B、C、D、E组各6只。A组第1天以生理盐水1 m L尾静脉一次性注射作为正常对照,B、C、D、E组均于第1天以尾静脉一次性注射NB混悬液1 m L建立大鼠草酸钙结石模型。A、B组第2天起均以生理盐水2m L/d灌胃,C、D、E组第2天起分别以0.05、0.10、0.15 g/m L乌梅提取物2 m L/d灌胃。各组干预4周后,收集24 h尿液,应用高锰酸钾褪色法测定尿液草酸(Ox)水平,全自动生化仪测定尿液Ca^(2+)水平,柠檬酸试剂盒测定尿液柠檬酸水平,8-羟基脱氧鸟苷(8-OHDG)测试盒测定尿液8-OHDG水平。取左侧肾脏,行HE染色观察肾组织草酸钙结晶形态,行结晶量分级评分。采用硫代巴比妥酸法检测肾组织丙二醛(MDA)水平。结果 B组尿液Ox、Ca^(2+)、8-OHDG水平均高于A组,柠檬酸水平低于A组(P均<0.05);C、D、E组尿液Ox、Ca^(2+)、8-OHDG水平均低于B组,柠檬酸水平均高于B组(P均<0.05)。A组无草酸钙结晶,B组草酸钙结晶明显较多,C、D、E组草酸钙结晶数量较B组明显减少。B组草酸钙结晶量评分高于A组,C、D、E组草酸钙结晶量评分均低于B组(P均<0.05)。B组肾组织MDA水平高于A组,D、E组肾组织MDA水平均低于B组(P均<0.05)。结论乌梅提取物对NB所致的大鼠肾草酸钙结石具有明显的抑制作用,其机制可能与降低大鼠尿液Ox水平,进而减少尿Ca^(2+)排泄、减轻脂质过氧化损伤有关。
基金Supported by the Khon Kaen University Research Fund in Thailand Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan
文摘AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.
