ABSTRACT
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by absolute or relative insufficiency of insulin secretion. As the disease progresses， patients begin to suffer from diabetic nephropathy， diabetic cardiomyopathy， non-alcoholic fatty liver disease or other complications， which increase the burden on the patients. Moreover， the number of patients is increasing， which brings a heavy burden to the society. Ferroptosis is a new type of programmed cell death which has attracted wide attention in recent years. It refers to the cell death caused by the excessive accumulation of lipid peroxide under the overload of iron ions. Studies have discovered that ferroptosis exists in diabetes mellitus and its complications. Inhibiting ferroptosis can greatly slow down the occurrence and progression of diabetes mellitus and its complications. Chinese medicine， the unique medical treasure in China， acts in a multi-pathway， multi-target manner and is praised for the cheap price， low toxicity， and mild side effects. It has been widely used in the treatment of diabetes mellitus and its complications and has demonstrated definite therapeutic effects， bringing the good news for the majority of patients. The regulation of ferroptosis by Chinese medicine may be a new direction for the treatment of diabetes mellitus and its complications in the future. This paper briefly describes the mechanism of ferroptosis， explores the relationship of ferroptosis with diabetes mellitus and its complications， summarizes the research status of Chinese medicine interventions， and puts forward suggestions， aiming to provide a reference for further research on the treatment of diabetes mellitus and its complications with Chinese medicine.
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ObjectiveTo observe the effect of Hedysari Radix polysaccharide （HRP） on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription protein 3 （STAT3） signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group， irbesartan group （irbesartan suspension， 22.75 mg·kg-1）， and high-， medium-， and low-dose HRP groups （HRP suspension， 200， 100， 50 mg·kg-1） according to the body weight， with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage， while those in the normal group and the model group received distilled water at 5 mL·kg-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid （UA）， triglycerides （TG）， and total cholesterol （TC） were detected. Periodic acid-Schiff （PAS） staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and mRNA expression levels of JAK2， STAT3， suppressor of cytokine signaling 3 （SOCS3）， and tumor necrosis factor-α （TNF-α） in the kidney. ResultAfter 12 weeks of treatment， compared with the normal group， the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA， TG， and TC levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA， TG， and TC levels （P<0.05， P<0.01）. Compared with the normal group， the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.05， P<0.01）. ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent， and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.
ABSTRACT
Diabetic nephropathy （DN）， as one of the common chronic microvascular complications of diabetes， has become the main cause of renal failure in end-stage renal disease in China， increasing the risks of renal dialysis and kidney transplantation in diabetes patients. It is the leading cause of death in people with diabetes. The latest research on DN has focused on the gene level. microRNAs （miRNAs） are a family of endogenous accessible short-chain non-coding RNA molecules. By acting on a particular target， they activate or inhibit its mediated signaling pathways and related molecules， playing an important role in the occurrence and development of DN. They have become microeconomic factors for the prevention and treatment of DN. Traditional Chinese medicine （TCM） has a long history in the diagnosis and treatment of DN and has unique advantages such as significant curative effect and few side effects. A large number of studies have proved that TCM can target miRNA to affect multiple signaling pathways， participate in the regulation of inflammatory response， pyroptosis， mesenchymal transdifferentiation， and other pathological changes， and delay the further development of DN. Therefore， this study discusses the biogenesis mechanism of miRNA and its action mechanism in disease-related signaling pathways based on TCM diagnosis and treatment approaches from the perspective of miRNA， and summarizes the effect of TCM targeting miRNA on the disease-related signaling pathways and on DN. Thus， this study is expected to provide a theoretical reference for exploring the progress of TCM intervention in DN from the perspective of genes.
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ObjectiveTo observe the effect of Hedysarum polysaccharides （HPS） on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group， irbesartan group， and high， middle， and low-dose HPS experimental groups according to their body mass， with 10 mice in each group， and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water， the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension， and the high， middle， and low-dose HPS experimental groups were given 200， 100， and 50 mg·kg-1·d-1 HPS suspensions， respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state， blood glucose （GLU）， 24 h urine protein （UTP）， blood creatinine （SCr）， and urea nitrogen （BUN） of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining （HE）. The protein and mRNA expression levels of Wnt1， β-catenin， glycogen synthesis kinase-3β （GSK-3β）， and phosphorylated GSK-3β （p-GSK-3β） in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultAfter treatment for 12 weeks， as compared with the normal group， the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU， 24 h UTP， SCr， and BUN in the model group increased （P<0.01）. As compared with the model group， the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent， and the levels of SCr， BUN， and 24 h UTP in the high and middle-dose HPS groups decreased （P<0.05，P<0.01）. As compared with the normal group， the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the model group were higher （P<0.01）， while the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group （P<0.05，P<0.01）. ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent， and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.
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Objective To observe the effects of hedysari polysaccharide (HPS) on myocardial fibrosis and the expression of MMP-2/TIMP-2 in model mice of diabetic cardiomyopathy; To discuss the mechanism of action of prevention and treatment of myocardial fibrosis in diabetes.Methods Sixty mice were randomly divided into model group, rosiglitazone group and HPS high-, mediume- and low-dose groups. The normal group was 12 non-transgenic male BKS.Cg-Dock7m+/+Leprdb/JNjumice with the same age. Each group was given relevant medicine for gavage, for 8 weeks. Blood glucose of mice before and after medication 2, 4, 6, and 8 weeks was detected. The levels of MMP-2, MMP-2 and MMP-9 in myocardium were measured by Masson staining. The protein expressions of MMP-2 and TIMP-1 in myocardium were detected by Western blot.Results Compared with the model group, the blood glucose of HPS (high- and medium dose) groups and rosiglitazone group decreased significantly. Masson staining showed that the green fibers in the model group significantly increased and rosiglitazone group and HPS high-dose group decreased compared with the model group. Western blot showed that the expressions of MMP-2 in model group and MMP-2/TIMP-2 ratio were declined significantly, while the expression of MMP-2 was increased and TIMP-2 was decreased significantly, and the ratio of MMP-2/TIMP-2 increased in rosiglitazone group and HPS high- and medium-dose group.Conclusion HPS may reduce the degree of myocardial fibrosis in model mice with diabetic cardiomyopathy. The therapeutic effect of HPS may be to relieve myocardial fibrosis in model mice by increasing the ratio of MMP-2/TIMP-2.
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Objective To observe the effects of Hedysari Polysaccharide (HPS) on the expressions of TSP-1 and PDGF-B in the retina of diabetic rats;To discuss the protective effect and possible mechanism on diabetic retinopathy. Methods The diabetic model was established by intraperitoneal injection of streptozotocin. 50 male SPF Wistar rats were randomly divided into 5 groups:model group, calcium dobesilate group, and HPS high-, medium-, and low-dose group, extra 10 rats were set as the normal group, 10 rats in each group. Each administration group was given relevant medicine for gavage, while model group and normal control group were given same amount NS for gavage, once a day for 8 weeks. The mRNA and protein expression of TSP-1 and PDGF-B were detected by qRT-PCR and immunohistochemistry. The retinal structure was observed by HE staining. Results HE staining showed that each layer of the retina of the model group was clear and complete, but the outer nucleus layer became looser, thinner and more disorderly, and the number of ganglion cells decreased slightly; the administration groups were improved markedly compared with the model group. Compared with the normal control group, the mRNA level and protein expression of retina TSP-1 on the model group dramatically dropped (P<0.01), and those of PDGF-B strikingly increased (P<0.01);Compared with the model group, the mRNA level and protein expression of retina TSP-1 on alladministration groups rose (P<0.05, P<0.01), and those of PDGF-B went down (P<0.01); Compared with all other administration groups, there was statistical significance in the mRNA level and protein expression of retina TSP-1 and PDGF-B on HPS high-dose group (P<0.05, P<0.01). Conclusion HPS may prevent the angiogenesis and proliferation in diabetic retinopathy process through adjusting the content of TSP-1 and PDGF-B in retina of diabetic rats so as to protect the retina.
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Objective To investigate the influence of hedysaryum polysaccharide (HPS)in the kidney function and expressions of Glut-1 mRNA and protein in kidney tissue of db/db mice with diabetic nephropathy (DN)and to elucidate its possible action mechanism.Methods 10 db/m mice were taken as normal control group(n=10);50 fueling animal model db/db mice with DN were randomly divided into model group,enalapril group and the low, middle and high doses of HPS groups(n=10).The mice in noral control group and model group were given physioloical saline by gavege;and the mice in the other groups were respectively given 10 mg·kg-1 ·d-1 enalapril, 100,200 and 400 mg·kg-1 ·d-1 HPS by gavage;lasted 8 weeks.Picric acid method was used to determine the serum creatinine(SCr)level of the mice,enzyme coupling rate method was used to determine the blood urea nitrogen (BUN)level,ELISA method was used to determine the urinary microalbumin(UMALB)level,RT-PCR method was performed to detect the expression of Glut-1 mRNA, and Western blotting and immunohistochemical methods were used to detect the expression of Glut-1 protein.Results Compared with model group,the levels of SCr, BUN, UMALB, the mRNA and protein of Glut-1 expressions were decreased, especially in 400 mg·kg-1 ·d-1 HPS and enalapril groups(P<0.01).The HE and Masson staining results showed that less inflammatory cells infiltration in glomerular of the mice were found, capillary lumens were unobstructed, and the collagen deposition was not obvious in 400 mg·kg-1 ·d-1 group.Conclusion HPS could improve the kidney function of the db/db mice and inhibit the Glut-1 mRNA and protein expressions obviously, which indicates that HPS could delay the development of DN by inhibiting the Glut-1 expression in the glomerular mesangial cell membrane.
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Objective To study the relationship between the retinal arteriosclerosis prevalence and related factors in in-service teachers from 3 universities. Methods The medical report of in-service teachers from 3 universities from July to October, 2012 were analyzed. Re-sults and Conclusion 2680 cases were included, in which 520 cases (19.4%) were diagnosed as retinal arteriosclerosis. Retinal arteriosclero-sis prevalence increased with age and cardiovascular risk factors. In the multi-factor logistic regression analysis, gender, age, hypertension, hyperlipidemia, impaired fasting glucose regulation, diabetes, hyperuricemia are independent risk factors for retinal arteriosclerosis.