| Objective The pathogenesis of CaOx stone is a gradually multifaceted process including crystal nucleation, growth, aggregation and retention. The prevalence of urinary stone ranged from 1% to 20% (average 10%) in the world wide due to various factors, such as geography, climate, race and diet. Minimally invasive techniques were widely applied in clinic so that many patients with urolithiasis gained an effective management. However, both the high recurrence rate and complications are so far a serious problem and remains to be decreased. Even though thiazide diuretics and alkali-citrate have been proven to be effective in reducing calciuria and stone recurrence, undesirable side-effects limit their use in long-term medical treatment. Therefore, finding an effective alternative with few adverse-effects is becoming a new tendency. Currently, there has been a sustained concern on medicinal plants to prevent stone recurrence owing to their efficiency, economy, and safety. Recently, the new drugs, which based on medicinal plants, such as Paclitaxel, Ginkgo biloba, Camptothecin, Artemisinin, and so on, are used in clinic and cause a resurgence of interest in medicinal plants. In traditional chinese medicine (TCM), Desmodium styracifolium (Ds) and Pyrrosiae petiolosa (Pp) have been widely used to release renal colic, hematuria, and remove stones. Additionally, our previous studies has shown that Lithium carbonate can significantly modulate endogenous citrate level according to lithium inhibit sodium dicarboxylate co-transporters (NaDC), which can transport citrate from tubular into cells. Due to calculus is the result of multifactor, we propose to increase citrate regulation through the combination the multi-target effect of chinese herbs and single target effect of LiC, enhance the prophylaxis of CaOx stones, select the optimal formula and clear its possible mechanism.Methods 80 adult male Wistar rats were randomly divided into eight groups (Normal, Control, LDs, MDs, HDs, LPp, MPp, and HPp). After one week of acclimatization, the rats were fed by containing 5% ammonium oxalate (AmOx) feed for one week, and then given the different does aqueous extracts(lml/time, Bid). On the 21st day of experimental period, the rats were placed in separate metabolic cages to collect 24-h urine, and then were anesthetized intraperitoneally with 10% Chloral Hydrate. Blood was obtained via inferior vena cava and then immediately excised kidneys. Samples were used to various determinations involving physical and biochemtry examination, pathological examination, crystalluria and CaOx deposition evaluation, OPN immunohistochemical staining, and oxidative stress studies.And then,90 adult male Wistar rats were randomly divided into eight groups (Normal, Placebo, LDs, MDs, HDs, LiC, LDs+LiC, MDs+LiC, HDs+LiC). The same interventions were 'used to treat the rats with the different doses aqueous extracts. The blood,24-h urine and kidneys were collected and used to various determinations involving physical and biochemtry examination, crystalluria, CaOx deposition evaluation and pathological examination.Results There were 3-fold increase in urinary Ox level and 5-fold decrease in Ca excretion in the urolithic rats.24h urinary volume, Ca, and Cit level were increased with varying degrees in the MDs and HDs group, and Ox concentration decreased (P<0.05). Not only was serum Ca distinctly decreased, but. also urinary Ca reduced in HPp group. In the normal group, no CaOx deposition was detected without pathological injury and CaOx crystalluria. OPN protein expression was weak and observed in the loop of Henle and papillary surface epithelium of few cells. Urolithic rats were observed more crystals dispositions in all parts of the kidney, especially in cortico-medullary junction, severe dilation of tubules and massive inflammatory infiltration, and more columnar whewellite and pyramidal weddellite crystals existed in urine. Scoring of crystal deposition showed a significantly lower number of deposits in MDs and HDs groups, but no statistic difference was concluded between two groups. In MDs and HDs groups, scoring of crystal deposition showed a significantly lower number of deposits, but no statistic difference was concluded between two groups. Pathological alteration reduced and has slight dilation of tubules and inflammatory infiltration. Simultaneously, OPN showed significantly lower expression than those in the urolithiatic rats. The mean number of crystals was distinctly reduced (MDs, HDs vs. Control:4.63±2.33,5.67±1.73 vs.14.6±3.72, P<0.001). Similar results as well as slight inflammatory infiltration were found in high dose Pp group. NO and MDA level rose rapidly, but SOD activities were inhibited in the control group (P<0.05). Although lower NO and higher SOD level were significantly observed in HDs and MPp groups, there was no Statistical significance in MDA. However, in MDs and HPp groups above three indicators restored to near normal levels. Serum Li was only detected in Lic and combination therapy groups, and showed a gradually increasing trend. Moreover, serum Li level was 1.38±0.41mmol/L in high dose combination therapy group. Urinary pH value, citrate, and calcium concentration significantly increased. Of these, urinary citrate level increased 53% and 24.3% compared with Ds and LiC groups, respectively. There was 1-fold increase in urinary volume and 1-fold decrease in Ox excretion. Crystal depositions were few, and its score showed a significantly lower number of deposits in MDs+LiC and HDs+LiC groups(P<0.05). The score of experiment groups except for LDs group demonstrated distinct reduction, and the score of MDs+LiC is lowest (0.78±0.67). Urinary crystals reduced to 1.11±1.05 and 1.38±1.06.Conclusions DS as a traditional antiurolithic herb indicates the beneficial effect on preventing renal stone formation at middle and high dose. They show diuretic action, citrate increase, Ox and Ca decrease, and antioxidative effect. However, given their similar effects, MDs is superior to HDs. High dose Pp shows significantly anti-inflammatory and antioxidative effects, and relatively weak prophylaxis of CaOx stone formation. The combination therapy middle dose Ds and LiC indicates obvious synergistic action on urinary citrate, which can increase 415%,53% and 24.3% compared with normal, Ds, and LiC groups, respectively. In addition, there is a beneficial effect on preventing renal stone formation when urinary volume, pH value and citrate increase, Ox decrease.
|
PDF Full Text Request