1.Clinical Analysis of Continuous Airway Positive Pressure Ventilation in Patients with Obstructive Sleep Apnea Syndrome Combined with Diabetes Mellitus
Zhigang LI ; Fengwen QIAN ; Ruzhong CUI
Tianjin Medical Journal 2014;(9):912-914
Objective To study the curative effect of continuous positive airway pressure (CPAP) on elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) complicated with diabetes mellitus. Methods Eighty patients with OSAHS and diabetes mellitus were included and randomly divided into treatment group (n=40) and control group (n=40). The control group was given conventional treatment including diabetes diet and hypoglycemic drugs. The treatment group was given Futong ST-25 continuous positive airway pressure (CPAP) ventilation besides the conventional treatment. The serum levels of fasting blood glucose (FBG), two-hour postprandial blood glucose (2 hPG), insulin, sleep apnea hypop-nea index (AHI), low oxygen saturation (LSpO2) and the longest apnea time were monitored before and after treatment in two groups. Results After four-week treatment, values of FPG, 2 hPG, AHI and the longest apnea time were significantly lower in treatment group than those in control group (P < 0.01), but values of insulin, two-hour postprandial insulin and LSpO2 were significantly higher in treatment group than those in control group (P<0.01). Conclusion CPAP therapy can effec-tively decrease blood sugar level and improve AHI, LSpO2 and the longest apnea time in elderly patients with OSAHS compli-cated with type 2 diabetes.
2.Effect of Dahuang Xiezhuo Prescription on Inflammation and SOCS3/TLR4 Pathway in Rats with Chronic Renal Failure
Xin XIN ; Zhenhua WU ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Qian ZHANG ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):95-104
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.
3.Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy
Meifang REN ; Zhenhua WU ; Fei GAO ; Guodong YUAN ; Qian ZHANG ; Xiaoling GUO ; Fengwen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):55-62
ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum (ER) stress and reducing urinary protein in the rat model of diabetic nephropathy (DN). MethodSeventy-five SD rats were randomized into normal, model, low-, medium-, and high-dose (4.37, 8.73, 17.46 g·kg-1, respectively) modified Shengjiangsan, and irbesartan (0.014 g·kg-1) groups, with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage, once a day, for 8 consecutive weeks. After the last administration, the levels of glucose (GLU) in the blood, 24-hour urinary protein (24 h-UTP), and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the renal tissue were measured. Hematoxylin-eosin staining, periodic acid-Schiff staining, and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin, podocin, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4) in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 (Sirt1), phosphorylated (p)-protein kinase RNA-like endoplasmic reticulum kinase (PERK), and p-eukaryotic translation initiation factor 2 alpha (eIF2α) in rat kidneys. ResultCompared with the normal group, the modeling caused pathological damage to the kidneys, elevated the levels of GLU and 24 h-UTP (P<0.05), up-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and down-regulated the protein level of Sirt1 (P<0.05) in rat kidneys. Compared with the model group, modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels (P<0.05), alleviated the pathological damage in the renal tissue, down-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and up-regulated the protein level of Sirt1 (P<0.05). ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue, thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.
4.Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia
Qian ZHANG ; Fengwen YANG ; Meng SHI ; Jinchang LIU ; Gang WANG ; Meifang REN ; Meijiao ZHAO ; Jingyu MAO ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):135-141
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.