| Background:Kidney stone is one of the most common urological disease in the world,with a worldwide incidence of 1%to 20%.In China,the incidence of the general population is 1%to 10%,of which 25%of patients need hospitalization.After the reform and opening up,with the improvement of living standard the incidence rate of kidney stones has increased greatly in our country,which has become one of the three countries with the highest incidence rate in the world.In southern provinces of China,renal calculi with kidney stones ranks almost the first in patients among urinary surgery.This undesirable growth trend has to be taken seriously by the urology surgeon.After the treatment of kidney stones,there are residual stones left and long term recurrence rate(60%-80%relapse rate within 15-20 years),so "removing residual stones and preventing stones" is significant for the prevention and treatment of renal calculi.In the clinical work,the author found that the majority of senile patients(age over 55 years)with kidney stone hospitalization had symptoms of deficiency of renal qi.After diagnosis and taking Jisheng renal qi pill,the curative effect improved obviously and the stone also had the reduction,thus this traditional Chinese medicine obtained many patients’ approval.Rejoice,we envisaged whether the Jisheng renal qi pill can solve the above problems(to excrete stones and prevent stones).We consulted the literature and did not find a study of the related "prevention and treatment" of kidney insufficiency.When using Chinese medicine to treat "urine barrier",we first reduce the heat,defecating urine,excreting stone,then enhance the kidney function to stabilize the fundamental.Chinese medicine theory holds that the excretion of stone is a "palliative".After the stone excretion,we should treat fundamentally,otherwise the kidney gas is still insufficient,and the body is still in an unbalanced state,thus there is a possibility of recurrence.This view is especially suitable for elderly patients with kidney stones.In modern medicine,the recurrence rate of calculi after kidney stone operation is very high.Although the stones are removed after operation,the adequacy of kidney qi should be further diagnosed.If omitted,the treatment and prognosis of kidney-qi-deficiency renal calculi are very unfavorable.Objective:So in the spirit of "saving lives,carry forward traditional Chinese medicine" duties,the author believes that it is necessary to verify the clinical efficacy(calculus excretion,stone prevention,symptom improvement),safety,adverse reactions and its mechanism of Jisheng renal qi pill in the treatment of renal calculi through clinical and experimental studies,in order to further explore the treatment of renal calculi with the characteristics of efficacy,its safety and possible mechanism of action.Method:1.Clinical research:Hospitalized patients who underwent PCNL surgery for kidney stones during June 2015 to February 2017 in Guangzhou TCM University First Subsidiary Hospital,aging above 55,TCM differentiation card belonging"kidney gas insufficient" type and met the diagnosis and the standard had formed the research.There were total 65 cases,which were made of 39 men and 26 women,average aging 60.Using random digital method,they were divided into the treatment group(Jisheng renal qi pill group of 34 cases)and the control group(sildenafil citrate acid potassium particles group of 31 cases).Both the treatment group and the control group took the prescribed drug for 7 months since the 7th day after PCNL.The two groups of patients were recorded in detail according to the relevant evaluation indexes including the signs,symptoms and efficacy indexes,liver function and adverse reactions before and after the treatment at 1st month,4th month,7th month(i.e.every 3 months).Data were collected and collated for statistical processing.2.The experimental research(1)Rats:62 SPF Male SD Rats,weighing 240g±20G.(2)The establishment of kidney-Qi deficiency syndrome in rats:① Poured warm water of 30 degrees to 40cm deep in a large plastic bucket with a volume of 20L,5 rats per barrel.Forcing the male rats to swim 3-5 times a day,Every time the rat was exhausted and sinking,the rat is fished out to rest for 15-20 minutes and put in the bucket again,2 consecutive weeks.The model of "QI deficiency" caused by excessive fatigue was induced.Analysis:Fatigue injures the spleen,excessive fatigue injures "QI".②Recorded Cat calls,played regularly to the rats every day of 1 to 1.5 hours,Volume>60 DB,at least 3 times a day,2 consecutive weeks.This method was used to stimulate the rat’ s fear of the sound source,resulting in "fear damaged kidney" model.③The two methods were combined for 2 consecutive weeks,which resulted in the syndrome model of "insufficiency of kidney qi" in rats.(3)Establishment and group-level administration of Kidney-Qi-deficiency renal calculi(calcium oxalate renal calculi)in rats:62 SPF Male SD rats were randomly divided into 6 groups on the basis of "kidney-qi deficiency" syndrome rat model.Respectively:The normal group has 10,the model group has 11,the traditional Chinese medicine low dosage Group has 10,the Chinese Medicine medium dosage Group has 10,the Chinese Medicine High dosage Group has 11,the positive control medicine(potassium citrate acid)group has 10.Finish 7 Days’ adaptive feeding,and start modeling from day eighthBlank group:Regular feeding(total 21 days);Model group:1%ethylene glycol free drinking water + 2%ammonium chloride perfusion(IG)2.6ml/rat/day+ 10%Calcium gluconate intraperitoneal injection 1.95ml/rat/day(total 21 days)→(Note:The following is said:Kidney stone method);Low dosage Group of Traditional Chinese Medicine:Kidney Stone method+ low dosage Chinese herbal Medicine(IG)(total 21 days);Medium dosage Group of Traditional Chinese Medicine:Kidney Stone method + medium dosage Chinese herbal Medicine(IG)(total 21 days);High dosage Group of Traditional Chinese Medicine:Kidney Stone method+ high dosage Chinese herbal Medicine(IG)(total 21 days);Positive drug control group:Kidney Stone method + positive drug(potassium citrate granules)perfusion Stomach(IG)(total 21 days),(4)Rat material and observation index:After 21 days of calcium oxalate kidney stone mold and drug delivery,6 groups of rats were weighed and recorded.The abdominal aorta blood was extracted and the serum was centrifugation,the right kidney was removed and the formaldehyde solution was fixed;Cut the left kidney and leave it fresh to spare.Serum sod activity,MDA content,blood creatinine Cr,blood urea nitrogen BUN,serum Ca2+ content were measured.The right kidney was stained with HE and made into pathological slices.The pathological changes of kidney and the adhesion deposition of calcium oxalate crystals were observed under microscope,and the number and distribution of the crystals were graded by " Class 0,Class I,Class II,Class Ⅲ,ClassⅣ".To take 1/4 left kidney,homogenate preparation,use the light amine method to measure sod activity and the content of MDATo take 1/4 left kidney,the expression of IKB,IKK,NF-KB and P65 in kidney tissue of rats was measured by Western Blotting assay technique,and the expression of 1L-1β in rat kidney tissues was measured by ELISA enzyme-linked immunosorbent assay.Results:1.Clinical results:Before treatment,the two groups were included in the sex,age,the number of residual stones after PCNL surgery,the diameter of stones,serum creatinine CR,urea nitrogen BUN,liver function ALT,AST,TBIL,kidney qi insufficiency of TCM syndromes,waist and abdomen pain,urine with blood,urine unfavorable,waist and knee limp and weak,tired fatigue,chills limb cold,face or limb edema,phlegm,cough and asthma and other indicators of the same baseline(p>0.05).In the 1st month,4th month and 7th month after treatment,the treatment group had no statistical difference in stone diameter(p>0.05)and other indexes such as:Residual stone quantity,the curative effect of serum creatinine CR,urea nitrogen BUN,deficiency of kidney qi,syndrome of TCM syndromes,waist and abdomen pain,blood in urine,adverse urination,weakness of waist and knees,fatigue and weakness,cold limb chills,facial or limb edema,phlegm and cough,asthma are obviously better than those in control group.The difference was statistically significant(p<0.05);During the 7-month course,the adverse reaction of the treatment group was significantly lower than that in the control group(p<0.05),and the cost of 7 months’medicine in treatment group is less than 3/10 of the Western medicine group,which could save more than 7/10(p<0.05).2.Animal experiment result:2.1 From the pathological sections of the kidney of rats,the relationship between the crystalline deposition of calcium oxalate and the pathological changes of renal tissue was discussed:Compared with the blank group,the model group had obvious crystallinedeposition(P<0.05),visible under the microscope:A large number of irregular morphological crystallization,renal tubular dilation is obvious,the glomerular appearance was irregular,the inflammatory cell infiltration was obvious,the cortical renal medulla was disordered.It showed that the method was successful and the rate of formation was high.The crystallinity and pathology of 3 dosage groups of Jisheng renal qi pill were different from that of model group,blank Group and Western Medicine group.In the middle dosage Group and high dosage Group of Chinese Medicine,the crystallization of the model group was decreased(P<0.05),and the high dose group had significant difference(P<0.01),which indicated that high and medium dosage of Chinese herbs could inhibit the formation of kidney stones,and the curative effect of high dose was significant.The low dose group compared with the model group(P>0.05)showed no obvious effect in inhibiting the formation of renal calculi.The Western medicine group compared with the model group(P<0.05)shows that it could inhibit the formation of kidney stones.The effect of high dosage Group and Western Medicine group on inhibiting the formation of renal calculi was similar(P>0.05).2.2 The contents of SOD activity,MDA content,SOD activity,MDA content,blood creatinine(Cr),blood urea nitrogen(BUN)and serum Ca2+were discussed in different groups of rats:The change trend of total sod activity and serum sod activity in renal tissue was consistent with the change of total MDA content and serum MDA content level in renal tissue.It was indicated that the relationship between local and whole is consistent,which jointly suggested the ability of scavenging oxygen free radicals,indicating the antioxidant capacity and oxidative damage.Comparison between model group and blank group:SOD activity and serum SOD activity of renal tissue were decreased(P<0.05),the content of MDA in renal tissue and serum MDA were increased(P<0.05),the blood Cr and blood BUN were increased(P<0.05),which indicated that the antioxidant capacity of the model group was decreased,the oxidative damage of renal tissue cells was aggravated,and the renal function was seriously damaged.Low dose group compared with model group:Total SOD activity,serum SOD activity,content of MDA in kidney,serum MDA content,serum creatinine Cr and blood urea nitrogen BUN and blood Ca2+ had no significant improvement(P>0.05),which showed that the low dosage group had no obvious curative effect in promoting the oxidative damage ability,protecting the kidney function and reducing the blood calcium in the risk factors of kidney stone formation in rats.The middle dosage group compared with the model group:Total SOD activity,serum sod activity,content of MDA,serum MDA content,blood creatinine Cr and blood urea nitrogen BUN and the Ca2+ of blood calcium were improved(P<0.05).It was indicated that the moderate dosage group had a certain curative effect in promoting the oxidative damage and protecting the kidney function of the rat kidney tissue cells,but there was no obvious curative effect in reducing the risk factors of renal calculi formation in Ca2+.High dose group compared with model group:Total SOD activity,serum SOD activity,content of MDA in kidney tissue,the serum MDA content,blood creatinine Cr and blood urea nitrogen BUN were obviously improved(P<0.01),which showed that higher dosage group had remarkable curative effect on improving antioxidant capacity and protecting renal function in renal tissue cells.The effect of reducing blood Ca2+ in this aspect was not obvious.Western medicine group compared with model group:The total SOD activity,serum SOD activity,total MDA content,serum MDA content and blood calcium Ca2+ in renal tissue were improved(p<0.05),it was indicated that the Western medicine group has obvious curative effect in promoting the antioxidant damage ability and reducing blood Ca2+ of the kidney tissue cells,but there was no significant difference between the blood Cr and Bun(P=0.081>0.05),indicating that the Western medicine group had no obvious curative effect in protecting the renal function.The middle dosage group compared with Western medicine group:There was no significant difference in improving antioxidant capacity of renal cells(P<0.05),the curative effect of renal function was better than that of Western medicine Group(P<0.05);There was no statistical difference in the efficacy of two groups in reducing blood calcium(P>0.05)High dose group compared with Western medicine group:There was a significant effect in improving the ability of renal tissue cells to resist oxidative damage(P<0.05),which was superior to Western Medicine Group(P<0.01)in the protection of kidney function,and there was no statistical difference between the two groups in reducing blood calcium(P>0.05).2.3 The expression of IKB,IKK,NF-KB,P65 in renal tissue of rats and the ELISA detection of 1L-1β in renal tissue were discussed:Comparison between model group and blank group:Factors in NF-KB pathway IKB’ s expression was lowered,the expression of IKK and NF-KB/P65 was increased,the expression of inflammatory factor 1L-1β was increased,and the statistics were significant(P<0.05),which showed that the method of modeling was successful and had caused inflammatory injury and inflammatory reaction in renal tissue.Compared with the model group,the medium dosage group and high dose group of Chinese medicine could increase the expression of the factor IKB in the NF-KB pathway.The expression of IKK and NF-KB/65 was reduced,the expression of inflammatory factor 1L-1β was reduced and the statistics were significant(P<0.05),the reaction medium dosage group had certain curative effect on inhibiting renal inflammatory injury,and the curative effect was more significant in High-dose group(P<0.01).Compared with the model group,there was no statistically significant difference in the expression of low dose group factor IKB,IKK and NF-KB/P65、1L-1β(P>0.05),which showed that low dose group had no obvious effect on inhibiting renal inflammatory injury.The Western medicine group compared with the model group:The above factor has the change(P<0.05),the reaction Western medicine group suppresses the kidney inflammation injury to have the certain curative effect.Compared with Western medicine group,the expression of factor IKB,the expression of IKK and NF-KB/P65 in NF-KB pathway of high dose group of Chinese medicine was improved,and the expression of inflammatory factor 1L-1β was similar(P<0.05),which showed that high dosage group had better effect on inhibiting renal inflammatory injury than Western medicine group.Conclusion:1.Clinical conclusionJisheng renal qi pill in the treatment of renal insufficiency type kidney stone patients can significantly reduce the number of residual stones,protect renal function(Cr ↓,Bun ↓),and have significantly improvement in kidney qi insufficiency of TCM syndromes,waist and abdomen pain,urine with blood,urine disadvantage,waist and knees limp and weak,exhaustion,fear cold limb cold,face or limb edema,phlegm drink cough and asthma symptoms.During the 7-month course,the incidence of adverse reactions was low and there were no toxic side effects.And the economic cost is less than 3/10 of the Western medicine group.2.Experimental conclusionJisheng renal qi pill has the ability to resist oxidative damage(SOD t,MDA ↓),resist inflammatory reactions(IKB ↑、IKK ↓、NF-KB ↓、P65 ↓、1L-1β↓),protect renal function(Cr ↓,Bun ↓,renal pathologic section crystallization deposition ↓,renal tissue damage ↓),and prevent stone.Jisheng renal qi pill may protect renal tubular epithelial cells and renal function through antioxidant injury(OS)and anti-inflammatory response(NF-KB pathway).Therefore,it is feasible and advantageous to Jisheng renal qi pill to treat renal insufficiency kidney stone,and it is worthy to be further studied and applied in clinic. |
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