三峡库区丹参中砷暴露对小鼠的肝肾毒性损伤研究

摘要

目的：探讨三峡库区丹参中重金属砷暴露对小鼠肝、肾的损伤情况及其毒性。方法35只昆明种小鼠随机分为正常对照组，丹参低、中、高剂量组和雄黄组，各7只。连续灌胃给药1周后，断头处死后取血及肝、肾组织，以全自动生化分析仪检测血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、尿素氮（BUN）和肌酐（Cr）含量，观察肝、肾组织病理学变化；电感耦合等离子体质谱（ICP-MS）法测定肝、肾组织中砷蓄积量；RT-PCR法检测砷毒性敏感基因金属硫蛋白-1（MT-1）mRNA表达水平。结果与正常对照组相比，雄黄组血清ALT，AST，BUN，Cr水平及肝、肾组织中砷蓄积量均显著升高（ P﹤0.05），并伴明显肝、肾损伤，金属硫蛋白-1( MT-1) mRNA表达量也显著升高（ P﹤0.05）。丹参各剂量组血清ALT，AST，BUN，Cr水平未见明显升高，仅高剂量组肝组织中检测到极微量砷，而低、中剂量组未检测到砷，且丹参各剂量组肾组织中亦未检测到砷。与正常对照组相比，丹参各剂量组病理学检查未见肝、肾异常，MT-1 mRNA表达量亦未见明显升高（ P﹥0.05）。结论丹参中所含砷的毒性远远小于雄黄的毒性，常规剂量给药是安全的。%Objective To investigate the injury situation of arsenic(As)exposure in salviae miltiorrhizae to liver and kidney in mice and its toxicity in Three Gorges Reservoir Area. Methods Totally 35 Kunming mice were randomly divided into the normal control group, low,middle,high doses salviae miltiorrhizae groups and realgar group. All the mice were given a week of intragastric administration sep-arately and executed by decollation to take the blood sample,liver and kidney tissues. Serum levels of ALT,AST,BUN and Cr were de-tected by using automatic biochemical analyzer. The histopathological changes of liver and kidney tissues were observed. The As accumu-lation amounts in the kidney and liver tissues were determined by using the ICP-MS. The As toxicity sensitive gene metallothionein-1 (MT-1) mRNA expression level was detected by RT-PCR. Results Compared with the normal control group,the levels of serum ALT,AST,BUN,Cr and As accumulation amounts in the liver and kidney tissues in the realgar group were significantly increased( P ﹤0. 05) and complicated by the obvious liver and kidney injury. The MT-1 mRNA expression level was significantly increased( P ﹤0. 05). The levels of serum ALT,AST,BUN,Cr in the various doses salviae miltiorrhizae groups had no significant increase,so did the MT-1 mRNA gene expression level. Only infinitesimal As was determined in the liver tissue of the high dose salviae miltiorrhizae group. No As was detected in the low and middle doses salviae miltiorrhizae groups,moreover no As was detected in the renal tissue of the various doses salviae miltiorrhizae groups;compared with the normal control group,no liver and kidney abnormality was found in the various doses salviae miltiorrhizae groups. Conclusion The As toxicity in salviae miltiorrhizae is much less than that in realgar and the conventional dose of salviae miltiorrhizae is safe.