1.Discussion on the Mechanism of Intervention of Dangui Hongqi Ultrafiltration in Diabetic Nephropathy Based on Lipophage Mediated mTOR/TFEB Signaling Pathway
Ting GAO ; Rongke LI ; Shengfang WAN ; Lei ZHANG ; Xiaolin ZHANG ; Qingquan XU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(6):66-72
Objective To explore the effect mechanism of lipophagy in diabetic nephropathy model rats based on intervention of Dangui Hongqi ultrafiltration in diabetic nephropathy model rats.Methods Fifty male Wistar rats of SPF grade were randomly selected 7 rats as the blank group,and the other 43 rats were given a one-time high-dose intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet to prepare diabetes nephropathy model.The modeling rats were randomly divided into model group,irbesartan group(17.9 mg/kg),and TCM low-,medium-,and high-dosage groups(1.5,3,6 g/kg).The rats were continuously gavaged by corresponding drugs for 12 weeks.Randomized blood glucose,body mass,and 24 h urine protein content were detected;biochemical tests were used for GSP,SCr,BUN,TG,TC,HDL-C,LDL-C,FFA content;HE staining was used to observe morphology changes in renal tissue,Masson staining was used to observe fibrosis changes in renal tissue,renal tissue microstructure changes were observed under transmisson electron microscopy,RT-qPCR was used to detect the mRNA expressions of mTOR and LC3B in renal tissue,and Western blot was used to detect the protein expressions of mTOR,TFEB,p-TFEB,and LC3B in renal tissue.Results Compared with the blank group,the model group rats showed a significant increase in randomized blood glucose(P<0.01),a significant decrease in body mass(P<0.01),a significant increase in 24 h urine protein content(P<0.01),a significant increase in GSP,SCr,BUN,TG,TC,LDL-C,FFA content(P<0.01),and a significant decrease in HDL-C content(P<0.01);renal tubular epithelial cells underwent vacuolar degeneration,cytoplasmic vacuolization,and extensive infiltration of inflammatory cells,collagen fibers increased and were distributed randomly,the number of lipid droplets increased,and autophagosomes decreased;the mTOR mRNA expressions in renal tissue significantly increased(P<0.01),the LC3B mRNA expressions significantly decreased(P<0.01),the mTOR and p-TFEB protein expressions significantly increased(P<0.01),the expression of TFEB,LC3BⅡ protein significantly decreased(P<0.01).Compared with the model group,the randomized blood glucose and 24 h urine protein content of rats in each treatment group were significantly reduced,the body mass significantly increased,and the contents of GSP,SCr,BUN,TG,TC,LDL-C,FFA decreased at 12 week of treatment,while the content of HDL-C increased;the inflammatory cell infiltration,fibrosis,and lipid droplet deposition in renal tissue alleviated to varying degrees;the expressions of mTOR mRNA decreased,the expressions of LC3B mRNA increased,the expressions of mTOR and p-TFEB protein decreased,while the expression of TFEB and LC3BⅡ protein increased.There was a statistically significant difference in the irbesartan group and TCM high-dosage group(P<0.01,P<0.05).Conclusion Dangui Hongqi ultrafiltration can improve the disorder of glucose and lipid metabolism,antagonize heterotopic lipid deposition in the kidney,promote lipid phagocytosis,and delay the process of diabetic nephropathy in model rats.The mechanism may be related to mTOR/TFEB signaling pathway.
2.Analysis of influenza and respiratory syncytial virus infection characteristics in children under 10 years of age in Gansu province in 2018
Deshan YU ; Shengfang FU ; Congshan XU ; Chao MA ; Hui ZHANG ; Wan WANG ; Jianhua CHEN ; Yue TANG ; Biaodi LI ; Yining ZHAO ; Hongyu LI ; Wenzhu GUAN ; Jian WANG
Chinese Journal of Experimental and Clinical Virology 2020;34(2):155-159
Objective:To study the epidemic and etiologic characteristics of influenza virus(Flu)and respiratory syncytial virus (RSV) infections in outpatient influenza-like illness(ILI)cases of children under 10 years of age in Gansu province in 2018 And to provide evidences for diagnosis, treatment, control and prevention of Flu and RSV infections in Gansu province.Methods:A total of 8 559 pharyngeal swab samples of ILI outpatients cases were tested with real-time fluorescent PCR to detect Flu, 3 436 of which were detected by RT-PCR for RSV.Results:Of the 8559 specimens, 934 (10.91%) samples were positive for Flu. Among them, 431 were positive for H1N1, 70 were positive for H3N2, 428 were positive for Flu B, 5 were mixed; 320 of the 3436 (9.31%, ) samples were positive for RSV. There were significant differences in the positive rates of Flu and RSV among 14 cities and prefectures ( χ2=56.99, χ2=263.34, Р< 0.01). Influenza reached its peak in January 2018 with a positive rate of 50.70%. Flu B/Yamagata strain (53.53%) and A H1N1 (39.93%) were prevalent simultaneously. The peak of RSV epidemic was from February to April, the positive rate was 13.98%. The RSV positive rate of children under 5 years of age was 10.11%, higher than that of children over 5 years of age was 6.94%. There was statistical significance ( χ2=7.67, Р<0.01). Conclusions:RSV and influenza viruses are the main pathogens in ILI cases of children under 10 years of age. There are epidemic peaks in winter and spring every year. It is suggested that the monitoring of RSV and the development and application of vaccine should be strengthened.
3.Hedysari Radix Polysaccharide Regulates Apoptosis of Smooth Muscle Cells in Gastric Antrum of Rat Model of Diabetic Gastroparesis via IGF-1/PI3K/Akt Signaling Pathway
Linlin MIAO ; Shengfang WAN ; Lei ZHANG ; Rongke LI ; Zhaohui WEI ; Xiaoli ZHU ; Hui AN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):130-139
ObjectiveTo observe the effects of Hedysari Radix polysaccharide on the apoptosis of gastric sinus smooth muscle cells and explore the underlying mechanism via the insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) pathway in the rat model of diabetic gastroparesis (DGP). MethodSixty-two Wistar male rats were randomized into a blank group (n=12) and a modelling group (n=50). The rat model of DGP was established by small-dose multiple intraperitoneal injections of streptozotocin combined with an irregular high-fat and high-sugar diet for 4 weeks. The modeled rats were randomized into model group, mosapride citrate (1.35 mg·kg-1), and high-, medium-, and low-dose (200, 100, and 50 mg·kg-1, respectively) Hedysari Radix polysaccharide groups. The rats were administrated with corresponding drugs by gavage, and those in the blank and model groups with equal volumes of pure water by gavage once a day for 8 consecutive weeks. The random blood glucose and body mass were measured every 2 weeks, and gastric emptying rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of smooth muscle in gastric antrum, and terminal deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) was employed to detect the apoptosis of smooth muscle cells in the gastric antrum. The expression of IGF-1, phosphorylated (p)-PI3K, and p-Akt in the smooth muscle of gastric sinus tissue was detected by immunohistochemistry. Western blot was employed to determine the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the smooth muscle of the gastric antrum. ResultCompared with the blank group, the model group showed elevated random blood glucose at all time points (P<0.01), decreased body mass and gastric emptying rate (P<0.01), increased apoptotic index of smooth muscle cells in the gastric antrum (P<0.01), down-regulated protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and up-regulated protein level of Bax (P<0.01). Compared with the model group, the 8 weeks of drug administration lowered the random blood glucose, increased the body mass and gastric emptying rate (P<0.05, P<0.01), decreased the apoptotic index of smooth muscle cells in the gastric antrum (P<0.05, P<0.01), up-regulated the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and down-regulated the protein level of Bax (P<0.05, P<0.01). Compared with the mosapride citrate group,the administration of low-dose Hedysari Radix polysaccharide for 6 and 8 weeks lowered the random blood glucose and decreased the body mass (P<0.05, P<0.01),low and medium-dose Hedysari Radix polysaccharide decreased the gastric emptying rate and the apoptotic index of smooth muscle cells in the astragaloside low-dose group decreased (P<0.05). The protein levels of IGF-1,p-PI3K/PI3K,p-Akt/Akt and Bcl-2(low dose)were down-regulated and the protein level of Bax was up-regulated by low doses of Hedysari Radix polysaccharide (P<0.05, P<0.01). Compared with high-dose Hedysari Radix polysaccharide, low-dose Hedysari Radix polysaccharide elevated random blood glucose and reduced body mass after 6 and 8 weeks of administration (P<0.05, P<0.01), and the low and medium doses decreased the gastric emptying rate, increased the apoptotic index of smooth muscle cells in the gastric antrum (P<0.05, P<0.01), down-regulated the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and up-regulated the protein level of Bax (P<0.05, P<0.01). Compared with the medium-dose group,the low-dose group of Hedysari Radix polysaccharide had lower body mass,lower gastric emptying rate in rats,higher apoptotic index of smooth muscle cells in gastric sinus tissue after 6 and 8 weeks of administration (P<0.05, P<0.01), and lower protein expression of IGF-1,p-PI3K/PI3K,p-Akt/Akt. ConclusionHedysari Radix polysaccharide protects the smooth muscle cells in gastric antrum against apoptotic injury and promotes gastric motility by activating the IGF-1/PI3K/Akt signaling pathway, as manifested by the up-regulated expression of IGF-1, p-PI3K, p-Akt, and Bcl-2 and down-regulated expression of Bax.
4.Mechanism of Chinese Medicine Against Diabetic Gastroparesis: A Review
Long LI ; Zhifeng TANG ; Wenjing SONG ; Fangyi CHEN ; Yuting YUE ; Xia YANG ; Zhigang WANG ; Wanxin ZHU ; Shengfang WAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):256-266
Diabetic gastroparesis (DGP) is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically, it often manifests as abdominal distension, nausea and vomiting, early satiety, dyspepsia, etc. The pathogenesis of DGP is multifactorial, closely related to many factors, such as chronic hyperglycemia, neuropathy, autonomic nervous system disorders, inflammation, and oxidative stress. These factors can interact with each other, leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine (TCM) has significant advantages in the prevention and treatment of DGP, including a long history, remarkable efficacy, individualized treatment, diverse therapeutic formulations, and improvement in the quality of life. Additionally, TCM is known for its low adverse reactions, good tolerance, and multi-targeted effects, making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones, inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and modulation of related signaling pathways such as stem cell factor (SCF)/cellular growth factor receptor (c-Kit), adenosine monophosphate-activated protein kinase (AMPK), Ras homologous genome member A (RhoA)/Rho-associated coiled-coil forming kinase (ROCK). This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and regulation of related signaling pathways, aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.