ABSTRACT
ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β2-microglobulin（β2-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.
ABSTRACT
OBJECTIVE:To observe the effects of Yishen huashi granules combined with Losartan potassium tablets on renal function indexes and inflammatory factors of patients with chronic glomerulonephritis. METHODS:A total of 107 patients with chronic glomerulonephritis in our hospital during Jan. 2015-Aug. 2016 were divided into observation group(53 cases)and control group(54 cases)according to therapy plan. Besides basic therapy,control group was given Losartan potassium tablets 50 mg,po, qd;observation group was additionally given Yishen huashi granules 10 g,po,tid,on the basis of control group. Both groups were treated for consecutive 2 mouths. Clinical efficacies,renal function indexes(Scr,BUN,24 h urine protein quantification,urine red blood cell)and inflammatory factors(IL-13,CRP,TNF-α)levels were all observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:Clinical total response rate of observation group(86.79%)was significantly higher than that of control group(66.67%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in renal function in-dexes or inflammatory factors levels between 2 groups(P>0.05).After treatment,renal function indexes and inflammatory factors levels of 2 groups were significantly decreased;and observation group was significantly lower than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Yishen huashi granules com-bined with Losartan potassium tablets in the treatment of chronic glomerulonephritis can improve renal function and reduce inflam-mation factor level with good safety.
ABSTRACT
OBJECTIVE:To observe the effects of Yishen huashi granules combined with Losartan potassium tablets on renal function indexes and inflammatory factors of patients with chronic glomerulonephritis. METHODS:A total of 107 patients with chronic glomerulonephritis in our hospital during Jan. 2015-Aug. 2016 were divided into observation group(53 cases)and control group(54 cases)according to therapy plan. Besides basic therapy,control group was given Losartan potassium tablets 50 mg,po, qd;observation group was additionally given Yishen huashi granules 10 g,po,tid,on the basis of control group. Both groups were treated for consecutive 2 mouths. Clinical efficacies,renal function indexes(Scr,BUN,24 h urine protein quantification,urine red blood cell)and inflammatory factors(IL-13,CRP,TNF-α)levels were all observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:Clinical total response rate of observation group(86.79%)was significantly higher than that of control group(66.67%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in renal function in-dexes or inflammatory factors levels between 2 groups(P>0.05).After treatment,renal function indexes and inflammatory factors levels of 2 groups were significantly decreased;and observation group was significantly lower than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Yishen huashi granules com-bined with Losartan potassium tablets in the treatment of chronic glomerulonephritis can improve renal function and reduce inflam-mation factor level with good safety.
ABSTRACT
OBJECTIVE:To evaluate the effectiveness and security of Yishen huashi granules in the adjuvant treatment of chronic nephritis systematically,and to provide evidenced-based reference. METHODS:Retrieved from CBM,CJFD,Wanfang database,VIP,Medline,PubMed,EMBase and Cochrane library,randomized controlled trials(RCTs)about Yishen huashi gran-ules in the treatment of chronic nephritis were collected and related magazines were retrieved by hand. After selection and data ex-traction by 2 researchers independently,the quality of included literature was evaluated according to Jadad rating scale,and Me-ta-analysis was conducted by using Rev Man 5.3.5 software. RESULTS:A total of 8 RCTs were included,involving 1028 patients. Total response rate of trial group [RR=1.33,95%CI(1.24,1.42),P<0.001] was significantly higher than that of control group. 24 h urine protein quantity [MD=-0.32,95%CI(-0.40,-0.24),P<0.001],serum creatinine [MD=-22.38,95%CI(-23.37,-21.39),P<0.001],blood urea nitrogen [MD=-1.45,95%CI(-2.05,-0.84),P<0.001] were significantly lower than control group,with statistical significance. CONCLUSIONS:Based on routine treatment,Yishen huashi granules have good therapeutic ef-ficacy for chronic nephritis,can reduce 24 h urine protein and improve renal function.