| Background and Objectives:Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone(PTH). Typically, it could be divided into three types, Primary hyperparathyroidism(PHPT), secondary hyperparathyroidism(SHPT) and tertiary hyperparathyroidism(3HPT). Parathyroidectomy is the most effective treatment options for most hyperparathyroidism with the feature of the abnormal proliferating glands, the limitation is the strict indications followed by operation, and some of the patients are not willing to accept the surgery. Further, missing or inadequate resection were usually occurred in patients with multiple or atypical adenoma, omission in which excessive removal may lead to persistent postoperative hypocalcemia, even permanent hypoparathyroidism. In recent years, minimally invasive surgery for the treatment of hyperparathyroidism is well developed for the advantages of small traumatic, good tolerance and low incidence of postoperative hypoparathyroidism, but it is just suitable for the patients with single adenoma.Photodynamic therapy(PDT) is a novel therapy based on photochemical reaction in recent years. The basic principle involved is that high concentration of photosensitizers can be accumulated differentially in some specific tissues, and reactive oxygen species(ROS) can be generated by light irradiation at specific wavelength(630nm) in the presence of oxygen. In turn, series of oxidative products can be produced, leading to cell death. And the goals to treat tumors and other diseases are achieved. Compared with the traditional surgery, radiotherapy, or chemotherapy, PDT showed more advantages of wide indications, high specificity, and less side effects, and has been widely used in the treatment of various tumors, skin diseases, and even infectious diseases. Studies have shown that the intermediate metabolite Protoporphyrin IX(Pp IX),a photoactive substance,was accumulated in normal and hyperplastic parathyroid tissues at higher concentration from the peripheral tissues after the administration of 5-aminolevulinic acid(5-ALA) into rat or human. But it remains unclear whether photodynamic effect was induced.The purpose of this study was to analyze the distribution feature of Pp IX in parathyroid tissue and its peripheral tissues in rat, and to identify the efficiency and safety of the effects of PDT on normal parathyroid. The application of PDT in the treatment of SHPT rat model was attempted, too.Methods1. PTG, TG, and the peripheral muscular tissues were cut after intraperitoneal injection of 5-ALA in rats. Concentrations of Pp IX were determined, respectively, and comparison was made in these tissues. At the same time, the relationship between Pp IX concentrations, the injection doses of ALA, or application duration was defined, respectively.2. Rats were randomly divided into groups according to the doses of photosensitizer and exposure duration. PTG and its peripheral tissues were exposed to photodynamic irradiation after operation. Serum levels of PTH, Ca, T3, T4,and TSH were measured before and after exposures and morphological changes of each tissue was observed.3. SHPT model rats were made after 5/6 renal resection combined with high phosphorus feeding, and was treated with PDT for several times. Changes of serum levels of PTH before and after each exposure were compared.Results1. Higher concentrations of PpIX were detected in PTG from that of its peripheral tissues at each time points; the concentration of Pp IX in PTG increased gradually with the application duration of 5-ALA(p<0.05), and the peak(77.38±8.92ug/g)was reached at 1.5 hours, followed by a gradual decline. Concentration of PpIX in PTG increased gradually with the doses of 5-ALA. When the dose of 5-ALA was increased from 400mg/kg to 600mg/kg, the increased level of PpIX in PTG was still observed, but with no statistical significance(p>0.05).2. No effect on parathyroid function was observed with the application of photosensitizer, or irradiation alone. There was a significant decrease in the serum levels of PTH and total Ca after irradiation for 0.25days(p<0.05), but no obvious alterations were detected in serum levels of T3, T4, and TSH before and after irradiation throughout the process(p>0.05). Serum level of PTH decreased with the increasing doses of 5-ALA and irradiation time, with a significant difference from control group(p<0.05); histological examination revealed an intact parathyroid tissue envelope after irradiation of PTD, but with a significantly decreased number of main cells and an increased number of fat cells. No significant change was found in TG and its peripheral muscular tissues.3. The serum levels of Cr and PTH were significantly higher in rats with 5/6 renal resection combined with high phosphorus feeding for 28 days than that before the operation(p<0.05). Serum levels of PTH were decreased with the increased numbers of irradiation of PDT in SHPT model rats. The serum level of PTH after three irradiations of PDT(100mg/kg,10min) was not different from that before operation(p>0.05).Conclusions:1. The accumulative concentration of PpIX in rat PTG mediated by ALA was obviously higher than that of the peripheral tissues, and was related with both doses injection and application duration of 5-ALA.2. The morphology and function of normal PTG could be specifically damaged by 5-ALA PDT, showing a better efficiency and safety.3. Therapeutic effects of 5-ALA PDT on SHPT model rats were significant, with a superimposition after repeated exposure. |
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