| Background Percutaneous coronary intervention(PCI)can effectively improve the prognosis and quality of life of patients with coronary heart disease,and is an important means of clinical treatment of coronary heart disease.However,postoperative complications such as contrast-related renal injury and contrast-induced nephropathy(CIN)have severely affected the postoperative recovery and prognosis of surgical patients.Contrast-related renal injury refers to impaired renal structure associated with the use of iodine contrast agents,with or without renal filtration function;when it develops into a severe phase,ie contrast nephropathy,is defined as serum creatinine in PCI Increased by 25% or 0.5 mg/dl(44 mmol/l)within 48 to 72 hours after surgery.With the extensive development of clinical diagnosis and treatment techniques such as angiography and coronary intervention(PCI),the probability of exposure to iodine contrast agents has increased significantly,and the number of patients with contrast-related renal impairment has also increased.Only contrast agent nephropathy That is,it has become the third most postoperative complications of PCI,and is also ranked third in the cause of acquired acute kidney injury in hospitals.At present,serum creatinine is often used as a diagnostic marker for contrast-induced renal injury and contrast nephropathy.However,serum creatinine is difficult to detect CIN early because of the late peak(3-5 days)and low sensitivity and easy to accept weight,age,sex,diet,body fluids,drugs and other non-renal factors.The patient has acute deterioration of renal function,and it does not recognize normal tubular tubular epithelial ischemic necrosis due to early contrast agent after PCI.This has delayed the early diagnosis and early treatment of patients with renal injury after PCI.Therefore,clinically needed markers of renal injury that are more sensitive and related to the pathogenesis of CIN are needed to reflect changes in renal function in patients with CIN.Phosphocreatine(Pcr),a major form of storage and transport of high-energy phosphates in human body,plays an important role in the cellular energy metabolism of various tissues and organs throughout the body.Our previous studies have confirmed its sodium salt form-exogenous Phosphocreatine sodium has protective effects on hypoxic-ischemic cardiomyocytes,and as a high-energy-consuming organ,whether Pcr has an effect on renal function is rarely reported in the literature,especially Pcr for contrast agent correlation.There is almost no research on whether kidney damage has a protective effect.Objective 1.To investigate the effect of exogenous sodium creatine phosphate on renal function in patients before coronary intervention,especially whether it can prevent the occurrence of contrast nephropathy.2.Through renal function indicators and kidney damage molecules such as creatinine(Scr),urea nitrogen(BUN),cystatin C(Cys-C)and glomerular filtration rate(eGFR)in the serum of the test subjects-Detection of novel renal injury markers such as 1(kim-1)and neutrophil gelatinase-associated lipocalin(NGAL),screening for the diagnosis and prediction of CIN and contrast-related renal function decline after PCI Diagnostic markers.Methods Eighty-two patients who underwent elective coronary intervention in the Department of Geriatric Cardiovascular Diseases,Qilu Hospital of Shandong University were enrolled.After obtaining their consent and signing the informed consent form for clinical trials,their medical records were recorded.According to the random number table method,and finely adjusted according to the principle of inter-group equilibrium,it was divided into control group and phosphocreatine(Pcr)group,41 cases in each group.All subjects included in this study were patients who underwent stenting after coronary angiography.In the control group,routine hydration treatment was given within 30 minutes before the operation.In the phosphocreatine group,4 g of exogenous sodium creatine phosphate and the same dose of normal saline were intravenously infused within 30 minutes before the operation.The serum levels of cystatin C,creatinine,urea nitrogen and other renal function indexes were measured before and after 4,8,12,24,36,and 48 hours after surgery,and MDRD glomerular filtration was used.The rate reduction formula calculates its eGFR estimate.Serum kim-1 content was determined using enzyme-linked immunosorbent assay(ELISA).At the same time,the effects of this dose of sodium creatine phosphate on liver function indexes,blood lipids and blood glucose in patients with postoperative ALT,AST,alkaline phosphatase and bilirubin were observed.The operation time,the type and amount of contrast agent,the number of diseased vessels and the placement of the stent were recorded in the PCI.The incidence of cardiac and cerebrovascular adverse events was recorded after PCI,such as postoperative angina pectoris,malignant arrhythmia,hypotension,ECG ST-T changes,cardiac function deterioration above grade I,stroke,cardiovascular death and so on.Results 1)Basic data: There were no significant differences between the two groups in terms of age,gender,combined disease(hypertension,heart failure grade,old myocardial infarction,diabetes)and surgical history(postoperative PCI).P >0.05).2)Data during PCI: There were no significant differences in PCI operation time,contrast agent dose,number of coronary artery counts,and number of stents placed in the two groups(P>0.05).3)incidence of cardiovascular adverse events after PCI: two groups of subjects had angina pectoris,malignant arrhythmia,hypotension,ECG ST-T changes,cardiac function deterioration above grade I,stroke,cardiovascular death,etc.There were no statistical differences in all aspects(P>0.05).3)Cystatin C: There was no statistical difference in Cys-C between the two groups before surgery,and it was homogenous(P >0.05).After repeated measures of variance analysis,the Cys-C levels of the two groups were statistically different between the 7 different time points before and after PCI(P = 0.031<0.05),between the time points within the same group.Comparing the postoperative 4 and 48 h of the Pcr group with the control group at 24 and 48 h after surgery,the baseline values were significantly lower than those of the control group(P = 0.048,0.036,<0.05,respectively),while the postoperative cystatin in the control group.There was no significant change in C concentration compared with preoperative(P>0.05).At 4 h after surgery,the effect value of Cys-C in the Pcr group(ΔCys-C,preoperative cystatin C concentration minus postoperative concentration)was significantly higher than that of the control group(P = 0.029<0.05),ie The level of pro-cystatin C in the Pcr group at this time was significantly lower than that in the control group.4)Serum creatinine and urea nitrogen: There was no significant difference in serum creatinine and urea nitrogen between the two groups at 7 time points(P >0.05).5)eGFR is calculated using the simplified formula of MDRD glomerular filtration rate: eGFR = 1.863 × serum creatinine-1.154 × age-0.203 ×(female × 0.742).There was no significant difference in eGFR between eGFR and eGFR between the two groups(P>0.05).6)kim-1: comparison of kim-1 levels at each time point,24 hours and 36 hours after operation in the control group were significantly higher than those before surgery(P = 0.046,0.037 <0.05),and kim-1 level group at each time point.In the comparison,the Pcr group was significantly lower than the control group at 4 hours(P = 0.048 < 0.05)and 24 hours(P = 0.036 < 0.05).7)Liver function,blood lipids,blood sugar: Liver function such as alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,bilirubin(total bilirubin,direct bilirubin)before and 4 hours and 24 hours after surgery There were no significant differences between the indicators and blood lipids(total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol)and blood glucose groups(P>0.05).Conclusion Exogenous sodium creatine phosphate has protective effect on the kidney of patients before coronary intervention,which reduces the incidence of contrast-induced renal injury and CIN.The incidence of adverse reactions is low and has high drug safety.Serum kim-1 and cystatin C showed earlier changes in renal injury and CIN after PCI,and had higher sensitivity.It can be used as an early diagnostic indicator of CIN after PCI and a marker of renal injury and renal insufficiency.Things.Background As the proportion of the elderly population in China has increased year by year,China has entered an aging society and has had a tremendous impact on all aspects of society and family.With the increase of age,the kidneys are particularly prominent in the functional changes of various organs in the human body.The renal function of the elderly caused by glomerular sclerosis,tubular atrophy and interstitial fibrosis can be reduced by 25%.P16 and p53 are important signaling proteins in two different signaling pathways in renal cell senescence,respectively.The expression level of p16 is related to stress-induced growth arrest,and the p53 pathway is a pathway in somatic senescence caused by telomere damage,P16 and The expression level of p53 in the kidney was positively correlated with the degree of renal aging.Oxidative stress is known to be a classic pathway for aging-related renal impairment and is closely related to energy metabolism disorders.L-carnitine and trimetazidine are two commonly used drugs in clinical practice to improve the energy supply of myocardial and skeletal muscle by regulating energy metabolism substrates.The former can enhance the aerobic oxidation of glucose,and the latter can promote the β-oxidation of fatty acids.There is no relevant research on the application of the two in kidney anti-aging.Objective To investigate the anti-aging effects of energy metabolism substrate regulation on kidneys of rats of different ages by administering exogenous trimetazidine and L-carnitine.Methods Wistar rats aged 3 months,19 months,and 24 months old were used as younger group(Young,Y),old age group(Aged,A),and older group(Old,O),respectively.One third of the rats were given Trimetazidine(T),L-carniting(L)and normal saline(Control,C)for 4 weeks,and were divided into 3×3 = 9 groups,respectively recorded as young control group(CY),young L-carnitine(LY),young trimetazidine group(QY),old control group(CA),aged L-carnitine group(LA),old trimetazidine group(QA),elderly control group(CO),aged L-carnitine group(LO),and old trimetazidine group(QO).The content of p16 and p53 protein in rat kidney tissue was detected by western experiment,and the morphology of rat kidney was observed by HE staining.Results 1.HE staining showed that with age,the aging characteristics of renal structure in CA group and CO group were more and more obvious than those in CY group,such as increased renal tubular degeneration and necrosis,interstitial inflammation and fibrosis,and small renal Cardiac hardening and expansion,tubular formation,etc.In the same age group,the aging characteristics of the trimetazidine group and the L-carnitine group were lower than those of the control group,and the aging characteristics of the L-carnitine group were less than those of the same age group.2.Western experiments showed that 1)the rats were given trimetazidine and L-carnitine two kinds of energy drugs,and the levels of p16 and p53 in the kidneys of CY,LY and QY rats were not statistically different.In the aged rats group and the old rats group,the levels of p16 and p53 in the LA group and the QA group were significantly lower than those in the LO group and the QO group(P<0.05).2).Compared with the control groups of different ages,the western results showed that the levels of p16 in CY group,CA group and CO group increased gradually,and the levels of p16 between CO group and CY group were statistically different.There was no statistical difference in p53 levels between CY group,CA group and CO group.The level of p53 in CO group was slightly higher than that in CA group,but both were lower than CY group(P>0.05).3.MDA and SOD test results display : 1)The serum MDA of CA group and CO group was significantly higher than that of CY group((P =0.037,0.025<0.05)).The serum MDA of LA group was significantly lower than that of CA group(P =0.046<0.05).The serum MDA of LO group compared with CO group.Significantly reduced(P =0.043< 0.05).2)The SOD of the CA group was significantly higher than that of the CY group(P =0.042<0.05).There was no statistical difference between the other groups.4)The liver function of rats in each group was compared,except for ALP,which was significantly higher than the old and old rats because of the growth and development of young rats.There was no statistical difference between the groups.The results of creatinine and urea nitrogen in the rats in each group were compared with the age,but the control group decreased with age,but there was no significant difference(P>0.05).Conclusion 1.By administering exogenous L-carnitine and trimetazidine to regulate the energy metabolism substrate of the kidney of aged rats,it can exert anti-aging effects on the kidney,and it has no adverse effects on liver and kidney function,and has higher Drug safety.The anti-renal aging effect of L-carnitine is more pronounced than that of trimetazidine.2.The anti-aging effects of L-carnitine and trimetazidine are closely related to the role of these two drugs in mitigating oxidative stress injury.3.L-carnitine and trimetazidine can down-regulate the senescence caused by p16-induced stress injury in rat kidney,and also down-regulate telomere and DNA damage represented by p53. |
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