OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,...OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway,thereby alleviating renal inflammation by inhibiting MCP-1,IL-6 expressions,and ameliorating renal fibrosis by inhibiting TGF-β1 expression.展开更多
Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-infl...Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P<0.05 or P<0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups(P>0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.展开更多
基金Joint Innovation Fundation of JIICM:Health Management of Chronic Kidney Disease Based on Integrated Traditional Chinese And Western Medicine(No.2021IR009)Natural Science Foundation-funded Project:the Mechanism of Modified Huangqi Chifeng Decoction Protect Damaged Podocyte via Cross-Talking of PI3K/AKT/mTOR and AMPK/mTOR/ULK1 Signaling Pathway Regulate Autophapy(No.81873300)+1 种基金the Central Publicinterest Scientific Institution Basal Research Fund of the China Academy of Chinese Medical Sciences:Comprehensive Evaluation of Clinical efficacy of Modified Huangqi Chifeng Decoction on IgA Nephropathy(No.ZZ11-023)the Beijing Municipal of Science and Technology Major Project:Evaluation of Clinical Efficacy of Modified Huangqi Chifeng Decoction in Treating Proteinuria in IgA Nephropathy Based on"Deficiency-Wind-Blood-Stasis-Toxicity"Mechanism in Chinese Medicine(No.Z191100006619063)。
文摘OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway,thereby alleviating renal inflammation by inhibiting MCP-1,IL-6 expressions,and ameliorating renal fibrosis by inhibiting TGF-β1 expression.
基金the National Natural Science Foundation of China(No.81960811)the Major Research Project of Innovation Group of Guizhou Provincial Department of Education(No.2018KY023)。
文摘Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P<0.05 or P<0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups(P>0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.
