| Objective:Urolithiasis is a common disease in urology,and its morbidity and recurrence rate remain high.It has a serious impact on the physical and mental health of patients,and it also troubles many clinicians.Its pathogenesis is still inconclusive,and in-depth research is necessary and urgent.Osteopontin(OPN)and the occurrence of urolithiasis,the PI3K-AKT pathway and the transformation and metabolism of renal tubular epithelial cells are the current research hotspots in the field of urolithiasis.Osteopontin is considered as an organic macromolecule.One of the matrix components of stone formation is essential in the stone formation stage,but the research on the pathway of osteopontin action is still in the exploratory stage.The view that renal tubular cell damage is an important risk factor for stone formation has been recognized by more and more scholars.At the same time,many studies have also shown that the PI3K-AKT pathway plays an important role in the transformation and metabolism of renal tubular epithelial cells.The method of clearing heat and eliminating dampness is widely used in the treatment of urolithiasis.Numerous studies have shown that the Miao medicine Polygonum capitatum has a definite effect in the treatment of urolithiasis.This study is based on the observation of the clinical efficacy of Polygonum capitatum on calcium oxalate stones and the study of its mechanism of action,exploring the relationship between osteopontin and the PI3K-AKT pathway,which may become a new breakthrough in the study of the mechanism of urolithiasis.Purpose:Based on the heat-clearing and dampening method,to explore the clinical efficacy and mechanism of Polygonum capitatum on calcium oxalate stones,and to provide experimental evidence for the treatment of urolithiasis with Polygonum capitatum.Method:Part 1:Using a randomized controlled clinical trial design method,72 patients with urolithiasis were selected and randomly divided into a treatment group and a control group using a random number table.Then compare the efficacy of Kelintong capsule combined with tamsulosin and tamsulosin for extracorporeal shock wave lithotripsy in the treatment of urolithiasis,and observe that Kelintong capsule can promote stone removal,reduce secondary lithotripsy,and reduce renal colic.Onset,reduce the use of antibiotics and analgesics,etc.Part 2:Focusing on the relationship between PI3K-AKT and osteopontin,42 male SD rats were selected and randomly divided into 7 groups:normal group,model group,low-dose group,medium-dose group,high-dose group,Kelintong group,and positive control group.After the rats have adapted to the environment for a week,the ethylene glycol modeling method is used to induce the formation of calcium oxalate stones in the rats.Through ELISA,HE staining,Western Blotting,immunohistochemistry and other methods,we observed the changes of urea nitrogen,creatinine,uric acid,urinary calcium,urinary citric acid,oxalic acid,crystallization of stones in the renal tubule lumen,PI3K-AKT pathway related protein and OPN protein changes in the rat’s 24h urine.These methods are used to explore the mechanism of Polygonum capitatum on calcium oxalate stones in rats.Result:Part 1:From the perspective of the effect of promoting stone removal,the total effective rate of the Kelintong group was significantly higher than that of the control group(P<0.05);From the perspective of the second lithotripsy rate,the second lithotripsy rate of the Kelintong group was significantly lower than that of the control group(P<0.05);From the number of days required for stone removal,the stone removal time of the Kelintong group was significantly lower than that of the control group(P<0.05);From the perspective of antibiotic usage rate and number of days of use,the antibiotic usage rate and number of days of use in the Kelintong group was significantly lower than that of the control group(P<0.05);From the point of view of analgesic usage rate,the analgesic usage rate of the Kelintong group was lower than that of the control group(P<0.05);From the scores of clinical symptoms in traditional Chinese medicine,the Kelintong group improved the symptoms of waist,abdomen and perineum pain,urination,hematuria,percussive pain in the kidney area,and ureteral stroke tenderness better than the control group(P<0.05);From the incidence of renal colic,there was no significant difference between the two groups of controls(P>0.05);From the incidence of adverse events,there was no significant difference between the two controls(P>0.05).Part 2:From the general state of the rat,after the establishment of the stone model,the weight of the rat is reduced,the amount of food is reduced,the body hair becomes sparse,the gloss of the body hair is reduced,the amount of activity is reduced,the fighting phenomenon is reduced,and the spirit becomes worse.From the results of 24-hour urinalysis in rats,the levels of calcium,oxalic acid,creatinine,urea nitrogen,and uric acid in the low-dose,middle-dose,high-dose and Klintong groups were lower than those in the model group(P<0.05).At the same time,the content of citric acid is higher than that of the model group(P>0.05).From the results of HE staining,the crystal scores of the low-dose group,middle-dose group,high-dose group and Klintong group were lower than the model group(P<0.05),especially the high-dose group and Klintong group.From the results of Western Blotting,the expression of PI3K in the low-dose group,middle-dose group,high-dose group and Klintong group was significantly higher than that of the model group(P<0.0001);The expression of AKT in the low-dose group,middle-dose group,high-dose group and Klintong group was higher than that of the model group(P<0.05),especially the high-dose group(P<0.0001);The expression of OPN in the low-dose group,middle-dose group,high-dose group and clintton group was lower than that of the model group(P<0.05),especially the high-dose group(P<0.0001).From the immunohistochemical test results,the expression of PI3K in the middle-dose group,high-dose group and Kelintong group was higher than that of the model group(P<0.05),especially the high-dose group(P<0.0001);The expression of AKT in the medium-dose group,high-dose group and Kelintong group was higher than that of the model group(P<0.05),especially the high-dose group(P<0.0001);The expression of OPN in the medium-dose group,high-dose group and Klintong group was lower than that of the model group(P<0.05),especially the high-dose group(P<0.0001).Conclusion:(1)Kelintong Capsule has obvious curative effect on urolithiasis(damp-heat stasis syndrome),which can reduce the secondary stone-elimination rate and antibiotic usage rate after extracorporeal lithotripsy treatment to a certain extent,and at the same time alleviate the pain during the stone-elimination process,It can significantly improve the symptoms of traditional Chinese medicine(waist,abdomen and perineum pain,urination,hematuria,percussive pain in the kidney area and tenderness of the ureter).(2)Polygonum capitatum and Polygonum capitatum drugs can reduce the urinary oxalic acid and calcium concentration in rats with calcium oxalate stones,increase the urinary citric acid concentration,reduce the damage of renal proximal tubule epithelial cells,and then have the effect of protecting the kidneys.(3)The action mechanism of Polygonum capitatum and Polygonum capitatum drugs in preventing and treating calcium oxalate stones may be related to its down-regulation of OPN expression.(4)Polygonum capitatum and Polygonum capitatum drugs alleviate the damage of renal proximal tubule epithelial cells,and then protect the kidney,which is related to the up-regulation of PI3K and AKT expression. |
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