RESUMO
ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg-1） and Niaoduqing Granules group （2.6 g·kg-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.
RESUMO
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α1-microglobulin （α1-MG）， urinary β2-microglobulin （β2-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ2 =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α1-MG， β2-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.
RESUMO
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the changes in renal pathology and reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor protein 3 （NLRP3） pathway expression in the kidney tissues of rats with 5/6 nephrectomy， and to explore the mechanism of Dahuang Xiezhuo prescription in protecting renal function and delaying renal interstitial fibrosis and the possibility. MethodNinety healthy male SD rats were randomly divided into a sham operation group， a model group， low， medium， and high-dose （6.825， 13.65， 27.30 g·kg-1） Dahuang Xiezhuo prescription groups， and a Niaoduqing granule group （2.60 g·kg-1）. Except the sham operation group， 5/6 nephrectomy was used to replicate the rat model of chronic renal failure （CRF）. After modeling， each administration group was given the corresponding dose of drug suspension by intragastric administration， once a day for consecutive 8 weeks. After administration， serum creatinine （SCr） and urea nitrogen （BUN） levels and 24 h urinary protein quantification （UTP） levels were detected. Western blot assay was used to detect the protein expressions of thioredoxin （TRX）， TXNIP， and NLRP3. The protein expressions of TRX， TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， transformation growth factor-β （TGF-β）， Collagen Ⅳ， α-smooth muscle actin （α-SMA）， and fibronectin （FN） were detected by immunohistochemistry. ResultAs compared with the sham operation group， serum levels of SCr， BUN， and UTP in the model group were increased （P<0.05）， TRX， TXNIP， NLRP3， ASC， TGF-β， Collagen Ⅳ， α-SMA， and FN proteins were increased （P<0.01）， and renal interstitial fibrosis significantly occurred. As compared with the model group， the levels of SCr， 24 h BUN， and UTP in the low， medium， and high-dose Dahuang Xiezhuo prescription groups and the Niaoduqing granule group were decreased to varying degrees （P<0.05）， TRX， TXNIP， NLRP3， ASC， TGF-β， Collagen Ⅳ， α-SMA， and FN were decreased （P<0.01）， and renal interstitial fibrosis was improved to varying degrees. ConclusionDahuang Xiezhuo prescription can protect renal function and delay renal interstitial fibrosis in rats with CRF.