ABSTRACT
ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.
ABSTRACT
Diabetic nephropathy （DN） is a common clinical complication of diabetes， the main cause of end-stage renal disease （ESRD）， and a key determinant of survival in diabetic patients. The pathogenesis of DN is complex， and it is currently believed to be associated with hemodynamic abnormalities， intestinal flora disturbances， glucose and lipid metabolism disorders， oxidative stress， genetic susceptibility， and protein non-enzymatic glycosylation. The local renin-angiotensin system （RAS） has always been the core of the pathogenic and progressive changes of DN. Once activated， it will induce the massive release of oxygen free radicals in the blood vessels， damage the endothelial function， and affect the microcirculation of the body. The recent studies demonstrate that intestinal flora and its metabolites may affect the occurrence and development of DN by activating or antagonizing the local RAS. Compared with western medicine treatment， traditional Chinese medicine （TCM） has the advantages of multiple targets and little toxic and side effects. Many TCM scholars have found that single herbs， their active ingredient extracts， and TCM compound prescriptions can improve kidney function by regulating the local RAS or intestinal flora. Specifically， the Chinese medicinal materials tonifying spleen （Codonopsis Radix， Dioscoreae Rhizoma， Atractylodis Macrocephalae Rhizoma， and Poria）， replenishing kidney （Rehmanniae Radix Praeparata， Corni Fructus， and Pseudostellariae Radix）， and activating blood， resolving stasis， and dredging collaterals （Hirudo， Salviae Miltiorrhizae Radix et Rhizoma， and Angelicae Sinensis Radix） have the regulatory effect. This article summarizes the roles of intestinal flora and local RAS in the occurrence and development of DN， and analyzes the animal experiments or clinical trials of TCM intervention in DN in recent years， aiming to provide more therapies and a theoretical basis for the treatment of DN with integrated TCM and Western medicine.
ABSTRACT
Objective To investigate related influencing factors in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 252 patients with T2DM who were treated in Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine from May 2021 to March 2022 were enrolled as subjects, and these patients were also included in Metabolic Management Center of China. According to the presence or absence of fatty liver disease, the patients were divided into simple T2DM group ( n =105) and T2DM+NAFLD group ( n =147). Related general data were analyzed, including sex, age, blood pressure, body height, body weight, neck circumference, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin, high-sensitivity C-reactive protein, albumin/creatinine ratio in morning urine, thyroid stimulating hormone, uric acid, intrahepatic fat deposition, carotid intima-media thickness, and brachial-ankle pulse wave velocity. The group t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was used to investigate the risk factors for T2DM with NAFLD, and the receiver operating characteristic (ROC) curve was used to assess the predictive value of related influencing factors. Results The age-stratified analysis showed that in the < 50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of body mass index (BMI), visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05); in the ≥50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of blood pressure, BMI, visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05) and a significantly lower level of serum HDL-C ( P < 0.05). The multivariate logistic regression analysis showed that BMI (odds ratio [ OR ]=1.408, 95% confidence interval [ CI ]: 1.136-1.746, P =0.002), HDL-C ( OR =0.031, 95% CI : 0.001-0.647, P =0.025), left brachial-ankle pulse wave velocity ( OR =1.003, 95% CI : 1.001-1.006, P =0.003), and uric acid ( OR =1.011, 95% CI : 1.005-1.016, P < 0.001) were independent influencing factors for T2DM with NAFLD. The ROC curve analysis showed that HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid had an area under the ROC curve of 0.695 (95% CI : 0.574-0.812), 0.708 (95% CI : 0.628-0.788), 0.611 (95% CI : 0.523-0.698), and 0.698 (95% CI : 0.617-0.779), respectively, in evaluating T2DM with NAFLD. Conclusion Low levels of HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid have a certain value in predicting NAFLD in patients with T2DM.