1.Role of SIRT1/Nrf2 signaling pathway in berberine-induced reduction of renal ischemia-reperfusion injury in mice
Linlin SUN ; Mingyue HAO ; Mingwei SHENG ; Jingshu LYU ; Yuhua YANG ; Jiahao ZHI ; Yiqi WENG ; Wenli YU ; Hongyin DU
Chinese Journal of Anesthesiology 2021;41(5):598-602
Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.
2.Comparison of myocardial protection in pediatric patients undergoing living-donor liver transplantation performed under propofol- versus desflurane-based anesthesia
Jiahao ZHI ; Yimei CAO ; Yingli CAO ; Hengchang REN ; Lili JIA ; Yiqi WENG ; Hongyin DU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(3):265-268
Objective:To compare the myocardial protection in pediatric patients undergoing living-donor liver transplantation (LDLT) performed under propofol- versus desflurane-based anesthesia. Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ pediatric patients of both sexes, aged 5-24 months, weighing 5-15 kg, scheduled for elective LDLT under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: propofol group (group P) and desflurane anesthesia group (group D). During anesthesia maintenance, propofol 5-10 mg·kg -1·min -1 was intravenously infused in group P, desflurane 0.65 MAC-1.30 MAC was inhaled in group D. At 5 min after induction of anesthesia, at 1 h of reperfusion, at the end of surgery, at 1, 2, 3, 7 and 14 days after surgery, and on the day of discharge, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase isoenzyme, N-terminal pro-B-type natriuretic peptide were determined by enzyme-linked immunosorbent assay, the occurrence of nausea and vomiting, agitation, and shivering, postoperative tracheal extubation time, intensive care unit stay time, and postoperative length of hospital stay were recorded within 24 h after surgery. Results:Compared with group P, the concentrations of serum high-sensitivity cardiac troponin I and creatine kinase isoenzyme were significantly decreased after surgery, the extubation time and intensive care unit stay time were shortened ( P<0.05), and no significant change was found in serum N-terminal pro-B-type natriuretic peptide concentrations, postoperative length of hospital stay and incidence of postoperative adverse effects at each time point in group D ( P>0.05). Conclusions:Desflurane has better myocardial protection than propofol in pediatric patients undergoing LDLT, which is helpful for early prognosis.
3.Clinical Efficacy and Transcriptomic Study on the Treatment of Coronary Heart Disease Angina of Qi Deficiency and Blood Sta-sis Type with Maitong Jun'an Decoction
Ziyang WANG ; Meizhi LIU ; Xiaozhen HU ; Miao ZHOU ; Jiahao WENG ; Zhikun LAI ; Yongning SUN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(4):419-428
OBJECTIVE To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease(CHD)angina of qi deficiency and blood stasis type,and preliminarily elucidate its possible mechanism of action through transcriptomics meth-ods.METHODS A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group,with 70 cases in each group.During the treatment period,3 patients in the control group dropped out.The control group received basic Western medicine treatment for secondary prevention of CHD,while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group.The treatment period for both groups was 8 weeks.Before and after treatment,the patients in both groups were evaluated for the TCM syndrome score,Canadian Cardiovascular Society(CCS)angina grading,Seattle angina questionnaire(SAQ)score,self-rating anxiety scale(SAS),self-rating depression scale(SDS)score,and adverse reactions.The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender,age,and disease duration matching.RESULTS After treatment,the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P<0.01).The treatment group was better than the control group in improving chest pain,chest tightness,shortness of breath,fatigue and total score(P<0.05,P<0.01);the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group(P<0.05);the SAQ,SAS and SDS scores of the 2 groups were significantly reduced before and after treatment(P<0.01),and the SAQ score of the treatment group was improved better than that of the control group(P<0.05,P<0.01).The transcriptomics results showed that there were 862 significantly different mR-NAs before and after treatment,including 509 up-regulated and 353 down-regulated.GO analysis showed that there were 666 biologi-cal processes in the differentially expressed mRNAs,mainly including viral gene expression,translation initiation,RNA catabolism,etc.There were 112 cell components,mainly including focal adhesion,ribosome subunit,nuclear spot,etc.There were 94 molecular functions,mainly including double-stranded RNA binding,cadherin binding,transcription co-regulatory factor activity,etc.KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways,mainly including glycerophospholipid me-tabolism pathway,AMPK signaling pathway,ribosome pathway,etc.CONCLUSION Maitong Jun'an Decoction can improve clini-cal symptoms in patients with CHD angina of qi deficiency and blood stasis type.Its mechanism of action is multi-target and multi pathway,mainly related to the regulation of glycerophospholipid metabolism pathway,AMPK signaling pathway,ribosome pathway.