| Renal interstitial fibrosis(RIF)is a common final pathway of most kinds of chronic kidney diseases(CKD)leading to end-stage renal failure(ESRD).Various kinds of pathogenic factors such as substantial accumulation of extracellular matrix(ECM)play a key role in the occurrence and development of RIF.Studies in current years have found that a variety of pro-inflammatory factors and inflammatory mediates are involved through the RIF.Oxidative stress and its mediated inflammations play an important role in RIF,which are important factors influencing the prognosis of CKD.Our previous study found that pathological changes during renal interstitial fibrosis were in accordance with the concept of"zhengjia" in TCM theory.And the increased synthesis and reduced degeneration of ECM in renal interstitium as well as balance disorder between generation and clearance of oxygen free radicals are also consistent with the theory of "Shenluozhengjia" theory and "Jusanshiheng"pathogenesis.Traditional Chinese medicine cordyceps cicadae,with similar effective ingredients as cordyceps sinensis,are a kind of high-quality cordyceps specie.Our previous study has shown that cordyceps cicadae,which can prevent and treat renal tubular interstitial fibrosis and also have the anti-aging effects,have become a hot spot in clinical and basic research of CKD.Objective:This paper aims to explore the curative effects of cordyceps cicadae in delaying the progression of CKD from clinical research and animal experiment,by observation on distribution characteristics of TCM syndromes in patients with CKD at stage 3-4 and on the curative effects of cordyceps cicadae on major syndromes,with patients with CKD at stage 3-4 and unilateral ureteral obstruction(UUO)models in rats as the research objects;so as to illuminate the internal mechanism of cordyceps cicadae in delaying the progression of RIF by intervention from oxidative stress and from inflammatory response.Methods:1.Clinical research:Patients with CKD at stage 3-4 were selected as the research objects to explore the distribution characteristics of traditional Chinese medicine syndromes.A prospective randomized control study was carried out on 66 patients for 30 days.Serum specimens were taken from two groups of patients before and after treatment,to analyze the changes of renal function,glomerular filtration rate,hepatic function,routine blood test,quantity of 24-hour urinary protein and serum IL-6 and TNF-α.2.Experimental research:SD rats were randomly distributed into sham-operation group,model group,cordyceps cicadae mycelium group,cordyceps sinensis group and benazepril group.Obstructive tubulointerstitial fibrosis was induced using UUO model.In the sham-operation group,the ureters were only separated rather than ligatured.At day 14 after surgery,serum and urine were collected,the animals were sacrificed and the obstructed kidneys were harvested.HE staining and Masson staining were used to observe pathological changes of rat renal tissues and immuno-histochemistry was used to detect the expressions ofα-SMA,FN,NF-κB,MCP-1 and TNF-α in rat renal tissues.RT-PCR was used to detect the mRNA expressions of NADPH p22phox.And serum creatinine(Scr),blood urea nitrogen(BUN),MDA,SOD and quantity of 24-hour urinary protein were tested.Results:Ⅰ.Clinical research1.Baseline conditions:(1)There were no significant differences between two groups of patients in baseline conditions,including gender,age,distribution of pathogenesis,chronic kidney disease(CKD)stage,distribution of TCM syndromes,blood pressure,renal function,hepatic function,blood lipid,hemoglobin,24-hour urinary protein quantity,and glomerular filtration rate.2.Influences of cordyceps cicadae therapy on renal function of CKD patients:(1)self-comparison in the same group showed in the control group,24-hour urinary protein quantity was significantly lower at the end of treatment course compared with before treatment,and there were significant differences in other indicators for renal function;while in the treatment group,Scr,BUN,MAD and 24-hour urinary protein quantity were significantly lower at the end of treatment course compared with before treatment.(2)After treatment,Scr and BUN of the treatment group were significantly lower than those of the control group,while the glomerular filtration rate was significantly higher than that of control group,and there was no significant difference in 24-hour urinary protein quantity.3.Influences of cordyceps cicadae therapy on serum inflammatory factors of CKD patients:(1)Before the treatment,serum IL-6 was obviously higher in the treatment group than that of the control group,but there were no significant difference in serum TNF-αbetween two groups.(2)Self-comparison in the same group showed in the control group,there were significant differences in serum IL-6 and TNF-α,but serum IL-6 and TNF-α in the treatment group were significantly lower at the end of treatment course compared with before treatment.(2)After treatment,there were no significant difference between two groups in IL-6 and TNF-α.4.Distribution characteristics of TCM syndromes in patients with CKD at stage 3-4 and the influences of cordyceps cicadae on major syndromes:(1)TCM syndrome characteristics of patients with CKD at stage 3-4 were the weakened body resistance as the root cause while pathogenic excess as the manifestation.And it was given priority to syndrome Pishenqixu,followed by Xueyu and Shire syndrome.(2)The influences of cordyceps cicadae therapy on renal functions of patients with Piqishenxu,Xueyu and Shire syndrome:Self-comparison in the same group showed that there were no significant differences in the renal functions and 24-hour urinary protein quantity of patients with Piqishenxu,Xueyu and Shire syndrome in the control group.But in the treatment group,the renal functions and 24-hour urinary protein quantity of patients with Piqishenxu,Xueyu and Shire syndrome were significantly lower at the end of treatment course.After treatment,Scr and BUN of the patients with Piqishenxu,Xueyu and Shire syndrome in the treatment group were obviously lower than those of the control group,while the glomerular filtration rate was significantly higher than the control group,but was not significantly different compared with the treatment group.(3)The influences of cordyceps cicadae therapy on serum inflammatory factors of patients with Piqishenxu,Xueyu and Shire syndrome:Self-comparison in the same group showed that there were no significant differences in the serum IL-6 and TNF-α of patients with Piqishenxu,Xueyu and Shire syndrome in the control group.But in the treatment group,the serum IL-6 and TNF-α of patients with Piqishenxu,Xueyu and Shire syndrome were significantly lower at the end of treatment course.After treatment,there were no significant differences between patients with Piqishenxu,Xueyu and Shire syndrome in the treatment group compared with the control group,and the treatment groupⅡ.Experimental research1.Influences of cordyceps cicadae therapy on renal function of UUO rats:Scr,BUN and 24-h urinary protein quantity of UUO rats in cordyceps cicadae group were significantly higher than that of the sham-operation group while significantly lower than that of the model group,but showed no significant difference with the cordyceps sinensis group;Scr and BUN of UUO rats in cordyceps cicadae group were significantly higher than that of the benazepril group,and there were no obvious difference between cordyceps cicadae group and benazepril group in 24-h urinary protein quantity.2.Influences of cordyceps cicadae therapy on RIF of UUO rats:The number of lost renal tubules and the degree of renal interstitial fibrosis in UUO rats of cordyceps cicadae group were significantly higher than those of the sham-operation group,lower than the model group,and not significantly different from the cordyceps sinensis group;RIF degree of UUO rats in cordyceps cicadae group was significantly lower than that of benazepril group,and the number of lost renal tubules was not significantly different compared with that of benazepril group.Expressions of α-SMA were significantly higher in renal tissues of UUO rats in cordyceps cicadae group than in sham-operation group,while significantly lower than in model group and benazepril group.And there was no significant difference compared with cordyceps sinensis group;FN expressions in renal tissues of UUO rats in cordyceps cicadae group were significantly higher than those of sham-operation group,lower than the model group,and of no significant difference compared with cordyceps sinensis group and benazepril group.3.Influences of cordyceps cicadae therapy on inflammatory response in renal tissues of UUO rats:Expressions of NF-κB in renal tissues of UUO rats were significantly lower in cordyceps cicadae group than those of model group,while of no significant difference compared with sham-operation group,cordyceps sinensis group and benazepril group.Expressions of MCP-1 in renal tissues of UUO rats were significantly higher in cordyceps cicadae group than those of sham-operation group,lower than those of model group,while of no significant difference compared with cordyceps sinensis group and benazepril group.Expressions of TNF-α in renal tissue of UUO rats were significantly higher in cordyceps cicadae group than those of sham-operation group,lower than those of model group,while of no significant difference compared with cordyceps sinensis group and benazepril group.4.Influences of cordyceps cicadae therapy on renal and serum oxidative stress of UUO rats:Expressions of serum MDA of UUO rats were significantly higher in cordyceps cicadae group than those of sham-operation group,lower than those of model group,while of no significant difference compared with cordyceps sinensis group and benazepril group.Expressions of serum SOD of UUO rats were significantly lower in cordyceps cicadae group than those of sham-operation group,obviously higher than those of model group,while of no significant difference compared with cordyceps sinensis group and benazepril group.mRNA expressions of p22phox in renal tissues of UUO rats were significantly lower in cordyceps cicadae group than those of sham-operation group,while of no significant difference compared with the sham-operation group,cordyceps sinensis group and benazepril group.mRNA expressions of p22phox were significantly enhanced in the model group compared with the sham-operation group.Conclusion:Cordyceps cicadae therapy can significantly reduce serum creatinine and blood urea nitrogen,as well as and reduce renal tubular damage and renal interstitial fibrosis,so as to delay the progression of CKD.And the mentioned roles may be played by reducing the release of inflammatory mediators,regulating the balance disorder between the generation and clearance of oxygen free radicals,and improving the level of oxidative stress.And the action mechanism of cordyceps cicadae in delaying the progression of chronic kidney disease(CKD is also consistent with the theory of "Shenluozhengjia" and "Jusanshiheng"pathogenesis... |
PDF Full Text Request