Xu Wangshu, Zhou Heng, Li Xiaojuan, Wang Lu, Guo Xinwu, Yin Linlin, Chang Haoxiao, Wei Yuzhen, Li Qingsong, Deng Jinhai, Zhou Xingang, Yang Haifeng, Zhang Xinghu, Yi Fang, Ma Wenping
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
Ann Transl Med. 2019 Jun;7(11):235. doi: 10.21037/atm.2019.05.01.
Herpes simplex encephalitis (HSE), an acute inflammatory disease of the central nervous system is caused by the herpes simplex virus infection. HSE occurs at any age, and it is often accompanied by high mortality and neurological dysfunction. The C1Q/TNF-related protein (CTRP) family, usually contains a homotrimeric structure, which comprises the N-terminal signal peptide and the C-terminal C1q globular domain. It has been demonstrated that CTRPs play pivotal roles in the inflammation process. CTRP4 is a member of the CTRP family and contains two C1q globular domains. Moreover, evidence shows that the recombinant human CTRP4 (rhCTRP4) protein exerts satisfactory anti-inflammatory effects in experimental colitis models via the NF-κB pathway. However, its role in inflammation-related neurological diseases remains unknown.
The purpose of this study is to evaluate the expression of CTRP4 and its correlation with HSE progression. We determined the serum CTRP4 levels in a normal brain, tuberculous meningitis (TBM), bacterial meningitis (BM) and HSE.
We found that compared to a normal brain, TBM and BM, CTRP4 was significantly increased in HSE. Moreover, in the course of HSE, serum interleukin (IL-6) and necrosis factor-α (TNF-α) were also increased and were closely associated with CTRP4 expression. CTRP4 expression was examined by immunohistochemistry (IHC) in the normal control brain tissues, HSE, TBM and BM brain tissues. High positively expression of CTRP4 was found in HSE. In the normal brain tissue, TBM, and BM brain tissues, CTRP4 showed a weak expression. In the clinical evaluation, CTRP4 expression correlated closely with an ascending stage of the disease [mini-mental state examination (MMSE) evaluation, MRI imaging).
Our findings suggest that CTRP4 is highly expressed in HSE and is closely related to the progression of HSE. Thus, CTRP4 may serve as a potential severity index for HSE and targeting CTRP4 might be a promising therapeutic strategy against HSE.
单纯疱疹病毒性脑炎（HSE）是一种由单纯疱疹病毒感染引起的中枢神经系统急性炎症性疾病。HSE可发生于任何年龄，常伴有高死亡率和神经功能障碍。C1Q/TNF相关蛋白（CTRP）家族通常包含一个同三聚体结构，由N端信号肽和C端C1q球状结构域组成。已证明CTRP在炎症过程中起关键作用。CTRP4是CTRP家族的成员，包含两个C1q球状结构域。此外，有证据表明重组人CTRP4（rhCTRP4）蛋白在实验性结肠炎模型中通过NF-κB途径发挥令人满意的抗炎作用。然而，其在炎症相关神经疾病中的作用尚不清楚。
本研究的目的是评估CTRP4的表达及其与HSE进展的相关性。我们测定了正常脑、结核性脑膜炎（TBM）、细菌性脑膜炎（BM）和HSE患者血清中的CTRP4水平。
我们发现，与正常脑、TBM和BM相比，HSE患者的CTRP4显著升高。此外，在HSE病程中，血清白细胞介素（IL-6）和肿瘤坏死因子-α（TNF-α）也升高，且与CTRP4表达密切相关。通过免疫组织化学（IHC）检测正常对照脑组织、HSE、TBM和BM脑组织中的CTRP4表达。在HSE中发现CTRP4呈高阳性表达。在正常脑组织、TBM和BM脑组织中，CTRP4表达较弱。在临床评估中，CTRP4表达与疾病进展阶段[简易精神状态检查（MMSE）评估、MRI成像]密切相关。
我们的研究结果表明，CTRP4在HSE中高表达，且与HSE的进展密切相关。因此，CTRP4可能作为HSE的潜在严重程度指标，靶向CTRP4可能是治疗HSE的一种有前景的治疗策略。
