中药药理与临床2026，Vol.42Issue(2)：50-57,8.
消肿止痛合剂通过TLR4信号通路对大鼠糖尿病神经痛的作用及机制
Xiaozhong Zhitong Mixture Treats Diabetic Neuropathic Pain in Rats through TLR4 Signaling Pathway
摘要
Abstract
Objective:To study the effect and mechanism of Xiaozhong Zhitong(消肿止痛)Mixture in the treat-ment of diabetic neuropathic pain(DNP).Methods:Forty male Sprague-Dawley(SD)rats were modeled for DNP via streptozotocin(STZ)and a high-fat high-sugar diet.The modeled rats were randomly assigned into model control,Xi-aozhong Zhitong Mixture(0.9 g/kg),Toll-like receptor 4(TLR4)inhibitor(TAK-242,3 mg/kg),and combined treat-ment(TAK-242 at 3 mg/kg+Xiaozhong Zhitong Mixture at 0.9 g/kg)groups(n=10).Another 10 rats were selected as the normal control group.Rats in each group were administrated with corresponding drugs or normal saline once per day for 14 consecutive days.The mechanical withdrawal threshold(MWT)and paw withdrawal latency(PWL)were measured.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the sciatic nerve tissue.Hematoxylin-eosin(HE)stai-ning was performed to examine the histopathological changes in the sciatic nerve tissue.The protein and mRNA levels of TLR4,nuclear factor-κB(NF-κB),and myeloid differentiation factor 88(MyD88)in the sciatic nerve tissue were quan-tified by Western blot and real-time PCR,respectively.Immunohistochemistry(IHC)was adopted to assess the positive expression of NOD-like receptor protein 3(NLRP3),cyclooxygenase-2(COX-2),and inducible nitric oxide synthase(iNOS)in the sciatic nerve tissue.Results:Compared with the normal control group,the model control group showed lo-cal breakage and sparse and uneven distribution of nerve fibers,widened myelin sheaths with segmental demyelination,lo-cal vascular dilation and lymphocyte infiltration,decreased MWT and PWL at different time points(P<0.05),up-regula-ted expression levels of NF-κB,MyD88,and TLR4 at both protein and mRNA levels(P<0.01),increased positive ex-pression of COX-2,INOS,and NLRP3(P<0.01),and raised levels of TNF-α,IL-6,and IL-1β(P<0.01).Compared with the model control group,the Xiaozhong Zhitong Mixture,TLR4 inhibitor(TAK-242),and combined treatment groups showed alleviated sciatic nerve damage,neatly and tightly arranged nerve fibers,no obvious lymphocyte infiltration,in-creased MWT and PWL(P<0.05),down-regulated mRNA levels of Nfκb,Myd88,and Tlr4(P<0.01),decreased posi-tive expression of COX-2,INOS,and NLRP3(P<0.05),and lowered levels of TNF-α,IL-6,and IL-1β(P<0.05).Compared with model control group,the Xiaozhong Zhitong Mixture and combined treatment groups showed down-regula-ted protein levels of TLR4,NF-κB,and MyD88(P<0.01),and the TLR4 inhibitor(TAK-242)group showed only down-regulated protein level of TLR4 in the sciatic nerve tissue(P<0.05).Overall,compared with the model control group,the combined treatment group showed the most significant changes in all indicators.Conclusion:Xiaozhong Zhi-tong Mixture can ameliorate the sciatic nerve injury,reduce inflammation and oxidative stress,and relieve the DNP pain in the rat model of DNP.Xiaozhong Zhitong Mixture combined with TLR4 inhibitor is more effective in ameliorating the sciatic nerve injury,reducing inflammation,and relieving DNP pain.关键词
消肿止痛合剂/信号通路/Toll样受体4/核因子κB/糖尿病/糖尿病神经痛/疼痛Key words
Xiaozhong Zhitong Mixture/Signaling pathway/Toll-like receptor 4(TLR4)/Nuclear factor(NF)-κB/Dia-betes/Diabetic neuropathic pain/Pain引用本文复制引用
刘涛,宋渊源,田慧卿,王威威,何志军,魏晓涛,何元旭,马岁录,何波,韩升龙,谢婧..消肿止痛合剂通过TLR4信号通路对大鼠糖尿病神经痛的作用及机制[J].中药药理与临床,2026,42(2):50-57,8.基金项目
国家自然科学基金项目(编号:81660802、82460942) （编号:81660802、82460942）
甘肃省青年人才个人项目(编号:2024QNGGR52) （编号:2024QNGGR52）
甘肃省自然科学基金项目(编号:22JR5RA620、25JRRA275、25JRRA269) （编号:22JR5RA620、25JRRA275、25JRRA269）
甘肃省重点研发计划项目(编号:21YF5FA021) （编号:21YF5FA021）
兰州市人才创新创业专项(编号:2019-RC-63) （编号:2019-RC-63）
甘肃省卫生健康科研行业项目(编号:GSWSKY2024-65、GSWSKY2024-15) （编号:GSWSKY2024-65、GSWSKY2024-15）
甘肃省青年科技基金计划项目(编号:21JR11RA211) （编号:21JR11RA211）
兰州市青年科技人才创新项目(编号:2024-QN-123) （编号:2024-QN-123）
甘肃省中医药管理局(编号:GZKZ-2024-3). （编号:GZKZ-2024-3）
