Yang Xiao, Zhu Lang-jing, Ji Yu-lian
Department of Nephrology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Jan;29(1):34-9.
To investigate the mRNA expressions of the TNF adapter proteins, including TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor-interacting protein 1 (RIP-1) and TNF receptor-associated factor-2 (TRAF-2) in peripheral blood mononuclear cells (PBMCs) of lupus nephritis (LN) patients of various TCM asthenia syndromes. Methods Fifty-one inpatients with LN were differentiated according to TCM syndrome differentiation, 13 cases of yin-deficiency with inner heat syndrome (A); 26 cases of both qi-yin deficiency syndrome (B), 12 cases of Pi-Shen yang-deficiency syndrome (C). Peripheral venous blood samples from the 51 LN patients and 17 healthy subjects were collected to separate PBMCs. The mRNA expressions of TNF adapter molecules (TRADD, FADD, RIP-1 and TRAF-2), as well as Caspase-3 and interleukin-1beta (IL-1beta) were analyzed by quantitative real-time PCR and the differences among them were compared.
(1) As compared with the healthy subjects, expression of TRADD mRNA in patients of syndrome A, B and C was lowered to 0.54, 0.32, and 0.38-fold, respectively (P < 0.05, P < 0.01), showing insignificant difference among the three syndromes; (2) FADD mRNA lowered to 0.79, 0.62, and 0.72-fold respectively, only with significance shown in syndrome B (P < 0.05); (3) RIP-1 mRNA lowered to 0.79, 0.50, and 0.60-fold respectively with significance shown in syndrome B and C (P < 0.01, P < 0.05), and insignificant difference was shown among the three syndromes; (4) TRAF-2 lowered to 0.70, 0.52, and 0.50-fold respectively (P < 0.01, P < 0.01, P = 0.07), significance shown in syndrome B and C (P < 0.01), but with insignificant difference among the three; (5) Caspase-3 elevated in all patients of the three syndromes (all P < 0.01); (6) IL-1beta in syndrome A was apparently lower ed to the normal range and also lower than that in the other two syndromes (both P < 0.05).
Expressions of TRADD, FADD, RIP-1 and TRAF-2 mRNA decreased in all the patients of various TCM asthenia syndromes, the decrement in patients of syndrome B and C was lesser than that in syndrome A. These abnormal low expressions of signal proteins might be the substantial bases for asthenia syndromes of LN patients, and the apoptotic signal mediated by them may involve in the formation of asthenia syndrome in LN.
探讨不同中医虚证类型的狼疮性肾炎（LN）患者外周血单个核细胞（PBMCs）中肿瘤坏死因子（TNF）衔接蛋白，包括TNF受体相关死亡结构域蛋白（TRADD）、Fas相关死亡结构域蛋白（FADD）、受体相互作用蛋白1（RIP-1）和TNF受体相关因子2（TRAF-2）的mRNA表达情况。方法 将51例LN住院患者按中医辨证分为阴虚内热证13例（A组）、气阴两虚证26例（B组）、脾肾阳虚证12例（C组）。采集51例LN患者及17名健康对照者的外周静脉血标本，分离PBMCs。采用实时荧光定量PCR法分析TNF衔接分子（TRADD、FADD、RIP-1和TRAF-2）以及半胱天冬酶-3（Caspase-3）和白细胞介素-1β（IL-1β）的mRNA表达，并比较其差异。
（1）与健康对照者比较，A、B、C组患者TRADD mRNA表达分别降至0.54、0.32和0.38倍（P<0.05，P<0.01），三组间差异无统计学意义；（2）FADD mRNA分别降至0.79、0.62和0.72倍，仅B组差异有统计学意义（P<0.05）；（3）RIP-1 mRNA分别降至0.79、0.50和0.60倍，B、C组差异有统计学意义（P<0.01，P<0.05），三组间差异无统计学意义；（4）TRAF-2分别降至0.70、0.52和0.50倍（P<0.01，P<0.01，P = 0.07），B、C组差异有统计学意义（P<0.01），三组间差异无统计学意义；（5）Caspase-3在三组患者中均升高（均P<0.01）；（6）A组IL-1β明显降至正常范围，且低于其他两组（均P<0.05）。
各中医虚证类型LN患者TRADD、FADD、RIP-1和TRAF-2 mRNA表达均降低，B、C组降低程度小于A组。这些信号蛋白的异常低表达可能是LN患者虚证的物质基础，其介导的凋亡信号可能参与LN虚证的形成。
