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ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.
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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.
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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.
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Objective:To investigate the correlation between hyponatremia and the severity of coronavirus disease 2019 (COVID-19).Methods:Clinical data of 12 patients with COVID-19 admitted to Shantou Central Hospital from January 23 to February 5 in 2020 were retrospectively analyzed, including gender, age, symptoms, lab test and clinical outcomes, to analyze the change trend of blood Na + level in the patients with COVID-19. Results:Among the 12 patients with COVID-19, there were 8 males and 4 females with the mean age of (38.0±16.3) years old, most of them were admitted to the hospital with cough and/or fever. All patients had a positive nucleic acid test for 2019 novel coronavirus (2019-nCoV), and were discharged after clinical treatment with oxygen therapy, antiviral, antibacterial, anti-inflammatory, and nutritional support. All patients were of ordinary type when they were admitted to the hospital. Among them, 1 patient turned into a severe case during the course of the disease, and 1 patient showed a tendency to become severe case. It was found that 10 patients without severe conversion had an average blood Na + of (138.3±1.3) mmol/L at admission, and the lowest blood Na + during the course of disease was (135.9±3.1) mmol/L. However, 2 patients who became severe and had a tendency to become severe disease (Na + levels at admission were 140.0 mmol/L and 138.0 mmol/L, respectively) experienced hyponatremia during the course of the disease (the lowest blood Na + levels were 129.0 mmol/L and 122.0 mmol/L). Further analysis showed that the lower serum Na + level, the higher level of white blood cell count (WBC) and C-reactive protein (CRP), but serum Na + level was consistent with the change trend of lymphocytes, suggesting that hyponatremia was closely correlated with severe inflammation reaction. Conclusions:Serum Na + showed decreasing tendency during the development of COVID-19, and hyponatremia was closely related to the severity of COVID-19. It was necessary to pay great attention to the change trend of blood Na + level. However, further research was needed to obtain more reliable conclusions and explorer the pathophysiological mechanisms.
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Objective To observe the effects of salvianolate on blood biochemical indexes, pathological changes of renal tissue and expression of CD2AP and Desmin protein in membranous nephropathy rats induced by cationic bovine serum albumin. And to explore the renal protective effect of salvianolate on membranous nephropathy rats and its possible mechanism. Methods Healthy male SD rats were randomly divided into normal group and modle group. Rat models of membranous nephropathy were reproduced by injection of cationized bovine serum albumin through tail vein. Model successful rats were randomly divided into model group, benazepril group, and salvianolate groups (16.7, 33.3, and 66.7 mg/kg). Each group was given the dose of the corresponding drugs. After treatment, the level of 24 h urine total protein (UTP), serum total cholesterol (TC), triglyceride (TG), total protein (TP), albumin (ALB), urea nitrogen (BUN), and serum creatinine (Scr) were detected. Immunofluorescence, light microscope, and electron microscope were used to observe the pathological changes of rat kidney. Immunohistochemistry and real-time PCR were used to detect the expression of CD2AP and Desmin. Results Compared with the control group, levels of UTP, TC, and TG increased significantly (P < 0.01), levels of serum TP and ALB decreased significantly (P < 0.01) in the model group. Compared with the model group, the UTP, TC, and TG of each treatment group were significantly decreased (P < 0.05, 0.01), while the TP and ALB were significantly increased (P < 0.01). There was no significant difference in the UTP, TC, TG, TP, and ALB among each dosage of salvianolate and benazepril group. And there was no significant difference among each dose group of salvianolate. There was no significant difference among each groups in the level of BUN and Scr. Compared with the normal group, the expression of CD2AP in model group was significantly decreased and Desmin was significantly increased (P < 0.01). Compared with the model group, the expression of CD2AP increased and Desmin decreased in each treatment group (P < 0.01), but there was no difference among the treatment groups. Conclusion Salvianolate has kidney protective effect on membranous nephropathy rats. The mechanism may be related to up-regulating the expression of CD2AP, down-regulating the expression of Desmin, inhibiting podocyte injury and protecting the integrity of the glomerular filtration barrier.
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Objective To compare the effect of high volume continuous blood purification (CBP) with routine CBP on multiple organ dysfunction syndrome(MODS).Methods 38 patients with MODS were randomly divided into high volume CBP group( treatment group,18 cases) and routine CBP group (control group,20 cases).And they were respectively detected on mean arterial pressure(MAP),dosage of Dopamine,PaO2/FiO2,APACHE [ score,lactic acid,length of stay and mortality in ICU post-treatment 24h and 48h.Results Compared with control group,MAP and PaO2/FiO2 on treatment group were more higher( P ＜ 0.05 ),while dosage of Dopamine,APACHE Ⅱ score,lactic acid were significantly shorter than these of treatment group( P ＜ 0.05 ),and length of stay and mortality in ICU were significantly lower than those of treatmen group [ ( 8.54 ± 4.15 ) d vs ( 11.82 ± 5.76) d,P ＜ 0.05:22.2％ vs 35.0％,P ＜0.05 ].Conclusion High volume CBP could reduce the mortality in ICU compared with control group routine CBP.