论文部分内容阅读
考察制首乌中易感物质顺式二苯乙烯苷(顺式-2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,cis-SG)转化量与特异质肝损伤的相关性,并探讨其可能的安全限度。通过光照将制首乌50%乙醇提取液中反式二苯乙烯苷(反式-2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,trans-SG)转化为cis-SG,得到不同转化量的样品,分别在正常大鼠和内毒素(2.8 mg·kg~(-1),iv)复制的易感性模型大鼠上给药(7.56 g·kg~(-1),ig),考察血浆生化指标、炎症因子及组织病理的改变等,比较大鼠肝损伤作用的差异。结果表明,所有制首乌样品在正常大鼠上均未引起肝损伤;在内毒素模型上,未光照、光转化cis-SG含量0.10%的制首乌样品均未见明显的肝损伤,而光转化cis-SG含量0.35%和0.70%的制首乌样品均引起明显肝脏病理改变,表现为肝细胞肿胀坏死、大量炎症细胞浸润,肝组织核转录因子-κB(NF-κB)p65表达量、细胞凋亡率均显著增加(P<0.05),同时血浆ALT、AST、TNF-α和IL-6含量均显著增加(P<0.05),过氧化物酶体增殖物激活受体-γ(PPAR-γ)含量显著降低(P<0.05)。同时,临床上制首乌引起肝损伤患者的余留药物含量分析发现,其cis-SG含量(>0.40%)均高于产地收集饮片(<0.10%)。综合实验评价和临床分析结果提示,易感物质cis-SG含量与制首乌特异质肝损伤存在一定的量-毒关系;为降低临床用药风险,初步建议可将cis-SG含量0.10%作为何首乌生产炮制过程的质控限度。
The conversion of cis-stilbene (cis-2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside, cis-SG) With specific liver injury and explore its possible safety margin. The trans-stilbene glycoside (trans-2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside, trans- SG) were transformed into cis-SG to get the samples with different conversion. The rats were treated with normal rat and endotoxin (2.8 mg · kg -1, iv) kg ~ (-1), ig). The changes of biochemical indexes, inflammatory factors and histopathological changes were investigated. The differences of liver injury in rats were compared. The results showed that all the samples of Radix notoginseng did not cause liver injury in normal rats. In the endotoxin model, there was no obvious liver damage in unprocessed Radix Polygoni The results showed that hepatocellular swelling and necrosis, inflammatory cell infiltration and the expression of nuclear factor-kappaB (NF-κB) p65 in hepatic tissues were significantly affected by the transformation of the samples with the content of cis-SG of 0.35% and 0.70% (P <0.05), meanwhile, the content of ALT, AST, TNF-α and IL-6 in plasma increased significantly (P <0.05) and the percentage of peroxisome proliferator activated receptor-γ -γ) content was significantly lower (P <0.05). Meanwhile, analysis of remaining drug content in patients with hepatic injury caused by Radix Polygonum multiflorum showed that the content of cis-SG (> 0.40%) was higher than that of the collected samples (<0.10%). Comprehensive experimental evaluation and clinical analysis suggest that there is a dose-toxicity relationship between the content of cis-SG of susceptible substance and the heterogeneity of hepatic injury in initial stage. In order to reduce the risk of clinical medication, it is suggested that the content of cis-SG should be 0.10% Polygonum production processing quality control limits.