四氯化碳 (CCl4)致急性肝损伤

Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl4)-induced acute
liver injury. Chondroitin-4-sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation ofnuclear factor (NF)-k B and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF-k B and apoptosis activation in
CCl4-induced liver injury in mice. Experimental approach: Acute hepatitis was induced in mice by an i.p. injection of CCl4. Varying doses of C4S were administered i.p. 1 h before,6 and 12 h after CCl4 injection.
24 h after CCl4 injection, the mice were killed for biochemical and histological analysis.,
活性氧(ROC) 是四氯化碳（CCl4）致急性肝损伤的主要原因-。

4-硫酸软骨（C4S）是通过抗氧化机制抑制脂质过氧化。

激活ofnuclear 因子(NF)-kB 和半胱氨酸蛋白酶强烈可能会加剧炎症和细胞的损伤，此外，直接施加的活性氧。

我们调查了C4S，除了发挥抗氧化活性，治疗是否能够调节Nf-kb 和凋亡活化在CCl4 诱导小鼠肝损伤。

实验方法：急性肝炎是小鼠腹腔注射致CCl4。

变剂量的C4S CCl4 注射后被管理的腹腔前6 和12 h 1 h。

24 h CCl4 注射后, 老鼠被杀的生化及组织学分析。

CCl4 injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels and depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF-k B translocation and IkB a, and increased gene expression of mRNA and protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of caspases-3 and -7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption. C4S treatment inhibited lipid peroxidation; blocked NF-k B activation and IkB a protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage. Conclusions and implications: As antioxidants may inhibit NF-k B and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF-k B and apoptosis activation in hepatic injury.
CCl4 注射制作：丙氨酸转氨酶和天冬氨酸转氨酶标志显著提升；肝膜脂质过氧化反应、化验由8-isoprostane还原型谷胱甘肽水平和减员超氧化物歧化酶。

CCl4 也下跌Nf-kb 移位和IkBa，和增加mRNA 和蛋白金属蛋白酶（MMP）-2 和-9，和pro 和半胱氨酸蛋白酶-3 的劈裂的形式及-7 基因表达。

也是弹性蛋白酶测定和肝细胞破碎评选的增加肝中性粒细胞浸润。

C4S 治疗抑制脂质过氧化作用；被阻止的Nf-kb 活化及IkBa 蛋白损失；减少mRNA 和蛋白为基质金属蛋白酶与半胱氨酸蛋白酶；已还原的内源性抗氧化剂；有限的肝多形核积累和组织损伤。

结论和所涉问题：如抗氧化剂可抑制Nf-kb 和半胱氨酸蛋白酶激活，我们推测C4S 治疗是能够抑制肝脏损伤Nf-kb 和凋亡激活。

Relaxin is a polypeptide hormone that triggers multiple signaling pathways through its receptor RXFP1. Many of relaxin’s functions, including vascular and ant fibrotic effects, are similar to those induced by activation of PPARγ. In this study, we tested the hypothesis that relaxin signaling through RXFP1 would activate PPARγactivity. In cells over expressing RXFP1 (HEK-RXFP1), relaxin increased transcriptional activity through a PPAR response element (PPRE) in a concentration dependent manner.
In cells lacking RXFP1, relaxin had no effect. Relaxin increased both the baseline activity and the response to the PPARγagonists rosiglitazone and 15d-PGJ2, but not to agonists of PPARαor PPARδ. In HEK-RXFP1 cells infected with adenovirus expressing PPARγ, relaxin increased transcriptional activity through PPRE, and this effect was blocked with an adenovirus expressing a dominant-negative PPARγ. Knockdown of PPARγusing siRNA resulted in a decrease in the response to both relaxin and rosiglitazone. Both relaxin and rosiglitazone increased expression of the PPARγtarget genes CD36 and LXRαin HEK-RXFP1 and in THP-1 cells naturally expressing RXFP1. Relaxin did not increase PPARγmRNA or protein levels. Treatment of cells with GW9662, an inhibitor of PPARγligand binding, effectively blocked rosiglitazone-induced PPARγactivation, but had no effect on relaxin activation of PPARγ. These results suggest that relaxin activates PPARγactivity, and increases the overall response in the presence PPARγagonists. This activation is dependent on the presence of RXFP1. Furthermore, relaxin activates PPARγvia a ligandindependent mechanism. These studies represent the first report that relaxin can activate the transcriptional activity of PPARγ.
松弛素是一种多肽激素,触发通过其 RXFP1 受体的信号通路。

许多的松弛素的功能，包括血管和抗纤维化效果，是类似于 PPARγ的激活所致。

在此研究中，我们测试信号通过 RXFP1，松弛素会激活 PPARγ活动的假说。

在细胞上表达 RXFP1 （曼浦汉克-RXFP1），松弛素浓度的依赖方式增加 PPAR 效应元件（PPRE）通过转录活性。

细胞缺乏 RXFP1，松弛素产生任何影响。

松弛素增加基线活动和响应 PPARγ受体激动剂罗格列酮和 15 d-PGJ2，但不是能受体激动剂的 PPARα或 PPARδ。

曼浦汉克 RXFP1 PPARγ腺病毒感染的细胞，在松弛素增加 PPRE，通过转录活性，而这种影响被阻止与腺病毒显性负 PPARγ。

PPARγ使用 siRNA 组合式导致松弛素与罗格列酮的回应的跌幅。

松弛素和罗格列酮增加 CD36 PPARγ目标基因的表达和 LXRα在细胞 RXFP1 和 THP 1 细胞自然表达 RXFP1。

松弛素不增加 PPARγ mRNA 或蛋白质水平。

GW9662，PPARγ配体结合，抑制因子与细胞治疗有效地阻止罗格列酮诱导 PPARγ激活，但对 PPARγ的松弛素激活并无影响。

这些结果表明，松弛素激活 PPARγ的活动，并会增加的整体反应中存在 PPARγ受体激动剂。

此激活是依赖于 RXFP1 的存在。

此外，松弛素激活 PPARγ通过 ligandindependent 机制。

这些研究代表该松弛素可以激活转录活性的 PPARγ的第一份报告。