【读文献 001】补体 C3 活化调节 tRNA 衍生片段 Gly-tRF 的产生，并促进酒精诱导的肝损伤和脂肪变性

本文链接：https://blog.csdn.net/hhhhhhaaaaaa1/article/details/130542940

Figure 1 C3敲除后可以治疗酒精性脂肪肝

1a 在减少C3方面使用C3基因敲除鼠和CR2-Crry(一种抑制C3活化的多肽）进行干预，检测血浆中C3a的含量来判断抑制效果

1b-1d 酒精性脂肪肝对应的表型检测

1e-1f 分别检测了血浆中TNFa和IL-6的含量以及肝脏中炎症因子得含量mRNA

CR2-Crry的文献

Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection - PubMed (nih.gov)

Figure 2 C3缺乏可以治疗肝脏缺血再灌注损伤

Figure 3 C3的产物ASP与C5aR2结合，进而C5aR2与β-arrestin2结合增加CYP2E1的表达-这里因果关系论证的很好

3a-3d 检测关键代谢酶CYP2E1是否受到影响，氧化应激是否改变

3e 回复实验，证明是C3导致了CYP2E1的改变，因果关系

The decreased expression of CYP2E1 in C3−/− mice was restored by treatment with the peptide C3a or its degraded form, C3a-des-Arg (also known as Asp), again indicating a causative link with C3 activation

3f 还是回复实验，ASP的作用是通过C5aR2

C5aR2 is the only identified receptor for Asp.

3g-3h 原来报道过的分子，β-arrestin2，动物水平上的IP实验和细胞敲除实验

3i-3j 还是用一点实验验证了一下原来报道过的CYP2E1分子的重要性

这里用了AAV9和药物两种方式

既往文献报道：Oxidative stress is a predominant factor that contributes to the pathogenesis of AFLD

细胞色素P450 2E1(cytochrome P450 2E1，CYP2E1)是一种主要位于肝细胞的化合物和毒物的代谢酶,是CYP450代谢酶系家族中的重要一员。它在酒精、四氯化碳、硫代乙酰胺、对乙酰氨基酚、二甲基亚硝胺等毒性底物的代谢和活化中起着重要作用[2-3]。诱导因子作用下，CYP2E1在氧化应激、活性氧簇产生以及酒精性肝损伤增强中可能是一个中心通路。

Figure 4 Gly-tRFs是引起酒精性脂肪肝的重要tRNA

4a-4c 找到关键的 tRNA Gly-tRFs-水平改变

4d Several studies have indicated that ANG induced by stress is involved in the biogenesis of tRF

ANG的改变引起的Gly-tRFs-水平（这个就是要与既往研究一致）

4e-4h Gly-tRFs抑制可以治疗酒精性脂肪肝

4i-4k 上述提及的分子均在Gly-tRFs上游，并具有因果关系

4l C5敲除并不影响Gly-tRFs的表达（为什么要加C5敲除鼠？）

Figure 5 探究Gly-tRFs的下游分子

5a 代谢变化-关键酶

5b sirt1含量变化

5c sirt1AAV9敲除表型检测

5d sirt1基因鼠表型检测

5e 和C3联系起来每个下游的分子都要和前面的关键分子联系起来

Hepatic tissues from mice treated with Gly-tRF inhibitors were subjected to transcriptome sequencing, and Gly-tRF was shown to be associated with lipid metabolism in AFLD mice 理由1 Gly-tRF inhibitors 后下游代谢发生很大变化

Previous studies have indicated that ethanol-induced attenuation of hepatic SIRT1 plays an important role in the pathogenesis of AFLD, and that stimulation of SIRT1 expression protected against the development of AFLD 理由2 SIRT1是控制下游代谢的关键转录因子（好的分子）

5h 之后都是找调控SIRT1的分子Ago3